The accident happened around 7:00 p.m. at East Girard and East Columbia Avenues.
Two cars collided with one car coming to rest against a fence and the other on its roof, police say.
The victims were taken to three area hospitals.
Police say, one victim was taken to Jefferson Hospital and is listed in critical condition.
Another victim, a 40-year-old woman was taken to Hahnemann and is listed as stable.
Two victims were taken to Temple Hospital. A 28-year-old woman is listed as stable and a 29-year-old is listed in serious condition.
The names of the victims have not been released.
Officials say, Columbia/Girard will be closed until sometime Monday.
Police continue to investigate.