All of those killed belong to the Shia religious group.
They are the latest victims in a wave of violence which has claimed dozens of lives there over the past few weeks.
Dera Ismail Khan borders the tribal region of South Waziristan where the Pakistani army is engaged in an operation against Taliban militants.
It provides the main route into the unstable region.
"The first incident took place at 11:00 this morning in the north of town," police chief Saeedullah Khan said.
Among these three victims two were named Ali and Zmat were brothers, shot dead at Islamia Colony by gunmen on motorcycles as they were standing outside their shop, while the 3rd victim named Bakth Wada was a taxi driver killed in Basti Diwala.
The local police chief said security had been tightened across the city in the wake of the incidents. It is said that security forces in the district appear unable to stop the killings.
They have been specifically targeted the Shia community, many of whom have already left the area. In recent days, Dera Ismail Khan has seen increasing numbers of pro-government Taliban militants on its streets, as reporters say.
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