The 18-year-old was in a street with a 17-year-old friend playing the popular augmented reality game on his smartphone when unidentified assailants on a motorbike shot at them on Monday.
They were attacked “for unknown reasons,” police said after gathering testimony from the friend, who was wounded but survived.
The killing happened in the town of Chiquimula in eastern Guatemala near the border with Honduras.
Police identified the victim as Jerson Lopez de Leon and said he and his friend had played Pokemon Go several times in the area.
“We can’t link this death to the Pokemon Go game,” a police spokesman, Jorge Aguilar, told AFP. He added that gang members were suspected of being behind the crime.
Violence, much of it related to gangs and drug trafficking, is rife in Guatemala and in neighboring Central American countries.