It happened just before 8 p.m. on the 1500 block of North Bouvier Street just blocks away from Temple University's campus.
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The injured victims include three women and two men.
Police say a 28-year-old man was shot 14 times. He is listed in extremely critical condition at an area hospital.
Chopper 6 over quintuple shooting in North Philadelphia
A 20-year-old woman is also listed as extremely critical after being shot seven times.
A 59-year-old man was shot one time in the chest and remains in critical condition.
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The two remaining victims, a 21-year-old woman and a 19-year-old woman, are both listed as stable.
Police arrested two suspects who were reportedly seen running from the crime scene. At least one weapon was recovered.
Philadelphia Police Captain John Walker pleaded with the community to come forward with tips.
"It's not like these people are not from this neighborhood. People know who these individuals are and they know who is responsible for this, and we're just asking: do the right thing," said Walker.
A spokesperson for Temple University says it does not appear any students were among the victims.
It's still unclear what sparked the shooting.
Anyone with information is asked to call police at 215-686-TIPS.