The centre-back, a regular for his country when fit, has been struggling with an ankle injury and had been rated only a 50-50 chance for the match in Amsterdam on Saturday evening.
The Scots remain hopeful he will be available for Wednesday's Group 9 match with Iceland at Hampden, but he will not travel to Amsterdam said Steven Pressley, one of manager George Burley's assistants. "Stephen did some light running today and was still feeling his ankle," Pressley reported.
Scotland have now had five players pull out of the match against the Dutch since the start of the week, with McManus joining his Celtic team-mate Paul Hartley, Rangers defenders David Weir and Kirk Broadfoot, and Derby County midfielder Kris Commons on the sidelines.
There was good news, however, concerning the condition of captain Barry Ferguson, who has been given the green light to play in Amsterdam after recovering sufficiently from bruised ribs.
"Barry Ferguson came through the late running okay and we are confident that he should make Saturday's game," said Pressley.
The two upcoming matches are likely to have a huge impact on Scotland's chances of reaching South Africa 2010.
The Netherlands, who top the group with nine points from a possible nine, look favourites to clinch the automatic qualifying spot, with Scotland, second with four points, battling Iceland, Norway and Macedonia for the play-off slot available to the runners-up.