Now they know the exact timeframe: He is suspended for more than half the season.
The star linebacker received his nine-game penalty from the league Friday stemming from a series of off-field legal issues.
A statement from the NFL said Smith had violated the NFL's substance abuse and personal conduct policies.
Smith won't be eligible to return until Nov. 10, the day after the 49ers' game against the New Orleans Saints.
''Our organization has known this decision would come and we have prepared for it as a team,'' 49ers general manager Trent Baalke said in a statement. ''Aldon has taken responsibility for his actions and has continued to show growth personally and professionally. We will continue to support him, but it is time to put this matter behind us and focus on the season ahead.''
The 24-year-old Smith, one of the NFL's top pass rushers, missed five games last season to undergo treatment at an in-patient facility following his DUI arrest Sept. 20.
It was unclear whether Commissioner Roger Goodell would consider that absence toward time served. Smith was suspended two days after Browns wide receiver Josh Gordon's indefinite suspension by the NFL was upheld and he will miss at least 16 games for another violation of the league's substance abuse policy.
Just before training camp began last month, Smith was sentenced to serve three years of probation and to spend 11 days with a work crew after he pleaded no contest to drunken driving and weapons charges.
He has repeatedly said he has been sober since his DUI arrest last September. Smith played in a 27-7 home loss to the Colts on Sept. 22, two days after he was arrested and jailed on suspicion of DUI and marijuana possession. After the game, he publicly apologized for his behavior and later announced he would leave for treatment.
While the Niners went on a five-game winning streak without him, Smith's menacing presence was sorely missed. The team still picked up his 2015 contract option this spring.
The 49ers, who went 14-5 last year and lost to the Super Bowl champion Seattle Seahawks in the NFC championship game, also are without injured All-Pro linebacker NaVorro Bowman for at least half the season as he recovers from a left knee injury that required surgery after the NFC title game.
Coach Jim Harbaugh and defensive coordinator Vic Fangio have expressed their confidence in the linebackers, who will be called upon to fill in with Bowman and Smith out - including rookie Chirs Borland, Dan Skuta, Michael Wilhoite and Corey Lemonier.
Third-round draft pick Borland made his case for a starting spot with a 34-yard interception return for a touchdown in Thursday night's 40-13 preseason win at Houston.
In his latest run-in with the law, Smith was arrested April 13 at Los Angeles International Airport. Police said Smith was randomly selected for a secondary screening and became uncooperative with the process, telling a TSA agent that he had a bomb. No charges were filed.
In November, he pleaded not guilty to three felony counts of illegal possession of an assault weapon, stemming from a June 2012 party at his home. Investigators said several shots were fired, two partygoers were injured and Smith was stabbed. In the subsequent investigation, prosecutors say detectives found five unregistered, illegal weapons in Smith's house.
Last season, Smith finished with 8 1/2 sacks and 34 tackles in 11 games with eight starts. He was initially worked back in slowly, but demonstrated he had stayed in shape while away.
Selected seventh overall in the 2011 draft out of Missouri, Smith had a franchise-record 19 1/2 sacks during the 2012 season for the 49ers, who lost to Baltimore in the Super Bowl after that season.
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