RCMP Cpl. Scott MacRae said the Nissan Altima was heading north on Highway 102 when the crash happened, at about 11:30 p.m. local time.
"Five people were in the car, two of them were ejected," MacRae said.
"Luckily, four people received non-life threatening injuries and were transported to hospital in Colchester. Unfortunately, one of the ejected females was transported by EHS LifeFlight to hospital in Halifax and remains in critical condition."
The people in the car are all between the ages of 20 and 21, and are believed to be foreign exchange students from Asia attending school in Antigonish.
Three lanes of Highway 102 — all southbound lanes and one northbound lane — were closed for several hours Saturday morning. The highway reopened at about 7:30 a.m.
MacRae said the crash is still under investigation.