Celtic kick off their campaign on Friday with a clash against Orlando Pirates in the MTN quarter-finals, and Larsen says Siwelele will pull through just fine as they face life without Mathoho, who recently joined Kaizer Chiefs.
"There was life before him and there will be life after him. It is part of the game that players and coaches come and go," Larsen tells KickOff.com.
"We have signed Dominic Isaacs and Brent Lawler from Chiefs, who I think are two very good defenders so they are capable replacements," he asserts.
"Bar his injuries, Dominic started 19 League games for Chiefs last season. He is a very consistent player in my opinion and every time he put on a Chiefs jersey he never let the team down, that's why we brought him to the team.
"He has started to gel very well with Thabo Nthethe and I'm hoping the partnership can develop into one of the best in the Premiership," the coach says.
Larsen is equally excited about the arrival of Botswana international winger Joel Mogorosi, who gave Bafana Bafana left-back Punch Masenamela a torrid time in a recent 2014 World Cup qualifier in Gaborone, and Larsen expects more of the same.
"I'm also expecting a big season from Joel and I think he will strike a lot of fear into quite a few fullbacks this season with his pace and skill.
"We must just get him 100 percent fit and he will be raring to go pretty soon," he adds.