The 31-year-old sustained a shoulder injury during the latter stages of Sunday's goalless draw against Kilmarnock in the Scottish Premiership.
Mannus was set to play in Northern Ireland's World Cup qualifier against Russia on Wednesday night but was forced to withdraw from the squad.
Saints have confirmed he is now set for an extended period on the sidelines, with player-coach Stevie Banks set to deputise in his absence.
A statement on the club's website read: "Tommy Wright has suffered a blow to his plans for the early part of the SPFL campaign with the news that goalkeeper Alan Mannus has been ruled out for up to six weeks with a shoulder injury.
"The Northern Ireland international keeper - he was due to make a competitive start for his country tonight until the call-off - suffered the injury in the late stages of Sunday's game at Kilmarnock with an opponent's foot catching him heavily underneath the arm at the joint with the shoulder.
"Scans have revealed damage which means the lengthy period of rest including an initial 10 days in a sling.
"Alan's absence paves the way for Stevie Banks to make an impact.
"The hugely experienced 42-year-old has close to 380 appearances in league matches alone in a lengthy career and took up a player/goalkeeping coach role at McDiarmid Park in the summer."