On 29 December 2014, Cafferkey, who had just returned to Glasgow from Sierra Leone via Casablanca Airport and London Heathrow Airport, was diagnosed with Ebola virus disease at Glasgow's Gartnavel General Hospital. She had been working at an Ebola treatment centre in Kerry Town in Sierra Leone, and it is thought she contracted the virus as a result of wearing a visor, as recommended by the World Health Organization and the UK Ministry of Defence, instead of goggles.
After initial treatment in Glasgow, she was transferred by air to RAF Northolt, then to the specialist high-level isolation unit at the Royal Free Hospital in London for longer-term treatment. A Scottish government spokesman described the risk to the general public as "extremely low to the point of negligible" due to the very early stage of the infection at the time of detection. Contact tracing was carried out on the other passengers who traveled on the flight from London to Glasgow with her. Medical staff described her condition at the time as "as well as we can hope for at this stage."
On 4 January 2015, the Royal Free Hospital announced that her condition had deteriorated to critical, with her health later stabilising before she was declared no longer critically ill on 12 January. Cafferkey received blood plasma from William Pooley and has been treated with experimental drugs as part of her treatment. On 24 January, she was declared to be free of infection, and released from hospital.
The prognosis after recovery from Ebola virus disease can include joint pains, muscular pain, skin peeling, or hair loss. In a media interview in September 2015, Cafferkey said "I’ve had trouble with my thyroid, lost some of my hair and get really sore joints but I guess side effects are to be expected."
It was found in 2015 that, after an apparent complete cure, with the bloodstream, saliva and organs such as the liver free of the Ebola virus, it can linger on in parts of the body not protected by the immune system, including fluid in the eye, the central nervous system and, in men, the testes and semen.
Cafferkey went to a 24-hour GP clinic in New Victoria Hospital in Glasgow on the night of 5 October 2015 and was diagnosed with "a virus" (unspecified) and sent home. 24 hours later she was admitted to Queen Elizabeth University Hospital where she was diagnosed with late complications caused by the Ebola virus hitherto considered unusual, and was flown by military jet to London, to the Royal Free Hospital. Her condition was initially described as serious and she was being treated in the high-level isolation unit. Doctors discovered that, after she had been deemed cured, the virus had remained in her cerebrospinal fluid and feared that it might be in her central nervous system. Personnel in Scotland monitored those whom she had come into contact with, since the virus can be spread through exposure to the infected person's body fluids, though they said the risk was likely to be small.
Her condition declined rapidly, and on 14 October 2015 she was reported to be critically ill. Five days later, on 19 October 2015, the Royal Free Hospital announced that: "Pauline Cafferkey's condition has improved to serious but stable".
On 21 October 2015 Dr Michael Jacobs, Cafferkey's doctor at the Royal Free Hospital, gave a televised press conference in which he explained that she has been suffering from meningitis caused by Ebola virus, and that she has not been re-infected with Ebola. He stated: "This is the original Ebola virus that she had many months ago, which has been lying inside the brain, replicating at a very low level probably, and has now re-emerged to cause this clinical illness of meningitis." He stated that this was unprecedented. Dr Jacobs went on to say that Cafferkey had "became critically ill due to neurological complications from the meningitis", and explained that she has been treated using a highly experimental anti-viral agent called GS5734, but he stressed that the crucial part of her treatment has been the exceptional nursing care which she is receiving. He said that "I'm really pleased to tell you that in the last few days she's made a significant improvement. She is much better now.", and that she has been talking to staff members, eating a little, and even using an iPad, although she remains in an isolation tent and is not well enough to get out of bed. He added that: "I think she has a long recovery ahead of her and will be with us for quite a while still."
On 12 November the Royal Free Hospital said that Cafferkey had made a full recovery and was no longer infectious. She was transferred to Glasgow's Queen Elizabeth University Hospital.
In February 2016, Cafferkey was admitted to Glasgow's Queen Elizabeth University Hospital after "routine monitoring by the Infectious Diseases Unit". On the same day she was transferred by a RAF plane to London where she was readmitted to the Royal Free Hospital. In a statement the Royal Free said she had been transferred to the hospital "due to a late complication from her previous infection by the Ebola virus" and that she was being treated by the hospital's infectious diseases team. On 24 February the hospital described her condition as "stable". On 28 February Cafferkey was discharged by the Royal Free Hospital. A spokesman said, "We can confirm that Pauline is not infectious. The Ebola virus can only be transmitted by direct contact with the blood or bodily fluids of an infected person while they are symptomatic."
On 6 October 2016 she was readmitted to the Queen Elizabeth University Hospital to be monitored by the infectious diseases team. A NHS Greater Glasgow and Clyde spokeswoman said that she was in a stable condition and undergoing investigations. In the evening of the same day a statement was issued stating that tests for the Ebola virus were negative.
In 2014, due to the fact that Cafferkey had passed through border controls and travelled on a domestic flight from Heathrow to Glasgow, criticism was levelled at current screening protocols at UK points of entry, which mainly consisted of taking a person's temperature and asking a series of questions. Public Health England stated that they were planning a review of the screening procedures.
In 2016, proceedings were initiated against Cafferkey by the Nursing and Midwifery Council alleging that she had allowed an incorrect temperature to be recorded during the screening process upon returning to the UK from Sierra Leone in 2014. Following a two-day hearing in Edinburgh during September 2016, the charges against Cafferkey were dismissed and she was cleared of any wrongdoing. The disciplinary panel was told that she had been impaired by illness at the time and heard evidence about how the Public Health England screening centre at Heathrow Airport had been unprepared for a large influx of passengers and that it was "busy, disorganised and even chaotic". BBC Scotland reporter Philip Sim wrote: "It now seems as if the case against Pauline Cafferkey had fallen apart before the hearing even began - raising questions as to why she had to go through it in the first place". In November 2016, a second panel criticised fellow volunteer senior nurse Donna Wood for suggesting "let's put it down as 37.2 and get out of here and sort it out later". Wood was suspended for two months for failing to alert the authorities about Cafferkey's condition.