"Following a urinary tract infection, septic shock and a cardio-circulatory collapse occurred," Vatican spokesman Joaquin Navarro-Valls said on Friday.
Sources in Rome told Aljazeera Pope John Paul's blood pressure had fallen drastically, signalling his health is entering a critical stage.
Earlier, Vatican sources said the Pope was receiving "appropriate antibiotic therapy".
The 84-year-old Pope has been convalescing from throat surgery for more than a month now and aides said earlier on Thursday he was disappointed by the slow pace of his recovery.
He underwent the tracheotomy on 24 February in Rome's Gemelli Hospital, where he spent a total of 28 days in two stints in February and March.
Doctors on Wednesday inserted a feeding tube through the Pope's nose and into his stomach to try to boost his strength and help his recovery. He has had a breathing tube in his throat since the 24 February operation.
Vatican officials said they were increasingly pessimistic about the Pope making a full recovery from his ailments.
"Hardly anyone thinks the situation will improve but everyone is hoping for a miracle," said one official.