The men were said to be riding motorcycles near Rafah close to the boundary with Israel.
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The Israeli military had been carrying out an operation in the area and come up against resistance from fighters using rockets and mortars.
Three more Palestinians were wounded in the attack, medical workers said.
Separately, two fighters of the Al-Quds Brigade were killed near El Bureij in central Gaza, where an Israeli military operation continued for a second day, the Islamic Jihad's armed wing said.
An Israeli army spokeswoman said soldiers fired at a group of armed men who had tried to plant a bomb near Israel's fence with the Gaza Strip.
One Israeli soldier was also wounded in the exchange.
Violence between Israeli forces and Palestinian groups has continued in the impoverished sliver of land despite attempts by Egypt to mediate a truce.