Police said three persons were fired upon in Orangi town and two of them died on the spot while one was seriously injured.
"Two of those killed belonged to the PPP," police official Tahir Naved said.
The southern Sindh province is governed by PPP.
Shooting incidents and target killings were also reported from other parts of the city in which eight people were killed.
The last few days have seen a surge in target killings in the city.
Sindh Chief Minister Syed Qaim Ali Shah has ordered an inquiry into the spate of target killings in the city.