Brown will require surgery and will join running back Ryan Matthews on the injured list for about eight weeks.
"It is definitely a blow," said tight end Antonio Gates.
The San Diego U-T said Brown broke his ankle making an 18-yard touchdown catch in the Chargers 28-20 preseason win over Dallas. He was taken off the field on a cart and penciled in for surgery Sunday.
Brown, who is in his second year in the NFL, had four catches and a touchdown in the preseason opener against Green Bay. Matthews went down in that game with a broken clavicle and will likely miss all of September.
The U-T said the Chargers would likely add another receiver to the roster to replace Brown, but might have to go with fewer special-teams players.