Fulham captain Tom Cairney picked up the ankle problem in Fulham’s 3-2 Premier League win over Burnley on Sunday.
The Fulham midfielder now faces up to a month on the sidelines.
Scots boss Alex McLeish is expected to name a replacement before he gathers his squad in Edinburgh on Sunday night.
The news will be a major blow for both club and country with Cairney having started all of Fulham's three games back in the Premier League.
Scotland will play against Belgium and Albania.