The attack targeted a gated residential building which mainly housed non-ethnic Somalis and non-Muslims, less than a kilometre from the volatile Somalia border town of Beled Hawa.
"We have suffered yet another attack in Mandera and sadly we have lost six people," Governor Ali Roba said in a statement.
Police chief Joseph Boinnet told AFP that there were 33 people inside the compound when the attack took place in the early hours of the morning.
"We highly suspect the attackers are members of the Shabaab insurgent group, who have sneaked across the porous border," he said.
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"These criminal gangs are desperate to hurt innocent Kenyans since they were defeated badly and routed out of all their hideouts in the neighbouring country."
Several bus ambushes in the region have seen gunmen separate passengers by religion, killing non-Muslims.
The Shabaab has fought to overthrow the internationally-backed government in Mogadishu since 2007, but turned its sights on Kenya when the army was sent into Somalia in 2011 to fight the Islamic insurgents.
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