This is Simpson's third NFL-issued suspension in four years, and this was for violating the league's substance-abuse policy last year with the Minnesota Vikings.
"The probability of a suspension was known when we signed Jerome," general manager Trent Baalke said in a statement. "Since joining the 49ers, Jerome has proven to be a great teammate.
"Although he will not be able to participate in the first six weeks of the season, Jerome has done everything asked of him, both on and off the field. We are in full support of the NFL's decision, and look forward to Jerome's future contributions to our organization."
After sitting out last season, Simpson has impressed upon joining the 49ers in March, both with his quick receiving skills on the field and proper behavior off it. Simpson had two catches for 31 yards in Saturday's exhibition opener at Houston, including a 25-yard catch. Simpson won't count against the 49ers' 53-man roster until he's eligible to come off suspension Oct. 19, a day after the 49ers host the Baltimore Ravens. He is able to continue practicing and playing through the final exhibition, Sept. 3 against San Diego, the story said.