Twiss went down injured in Saturday's defeat at Gravesend & Northfleet and is thought to have damaged medial ligaments.
"We will probably be without Michael for the season. He is a key player for us," Morecambe manager Sammy McIlroy told BBC.
"Losing a key player gives other teams a lift but we must overcome that."
Twiss has registered 14 goals for the Shrimps this season and will be a big loss as the club push for promotion during the latter stages of the campaign.
Source: http://www.confguide.com/newsArticle.do?id=5534