Hull defender Bruce was due to make his Northern Ireland debut after transferring his allegiance from the Republic of Ireland, but a groin strain has forced him to return home.
Meanwhile, McCann has sustained a knee injury meaning he will also miss the meeting with the second-placed Portuguese in Group F.
|SHOCK ON THE CARDS?
|55/1||Northern Ireland are 55/1 to beat Portugal 1-0 with Paddy Power|
Manager Michael O'Neill was already without the services of West Brom captain Chris Brunt and Derby’s Jamie Ward through injury.
Bruce’s Hull team-mate Joe Dudgeon, Newcastle’s Shane Ferguson, Burnley’s Martin Paterson and Hibernian’s James McPake have also all pulled out of the squad.
O’Neill has already drafted in Bradford’s Rory McArdle, Burnley’s Daniel Lafferty and Watford’s Lee Hodson, but will not be calling up additional replacements for Bruce and McCann.