Roberto Martinez has confirmed neither Thomas Meunier nor Jan Vertonghen are fit for international duty, but Kevin De Bruyne has returned to the Belgium squad.
The Red Devils, who have already qualified for Euro 2020, have limited defensive options for upcoming matches against Russia and Cyprus.
Wing-back Meunier suffered a thigh strain in Champions League action for Paris Saint-Germain against Club Brugge last month and is yet to return.
Meanwhile, Tottenham defender Vertonghen, who has struggled for form this season, was last seen on the bench at Liverpool at the end of October.
Vissel Kobe's Thomas Vermaelen is included but will be assessed as he deals with his own fitness issues, while Jason Denayer is brought in.
Anderlecht left-back Elias Cobbaut also profits from the various injuries, earning a first senior call-up.
"[Goalkeeper] Koen Casteels, Meunier and Vertonghen are injured," explained Martinez. "We are not sure if Vermaelen will be available. He will be assessed on Monday.
"Cobbaut has had a good transition with Johan Walem and the under-21s. The European Under-21 Championship last season was a key moment for him. For his club, he shows that he is growing all the time."
The return of De Bruyne is a boost, meanwhile, having last played for his country against Scotland in September due to a subsequent groin strain.
Brighton and Hove Albion forward Leandro Trossard is also fit again and in the squad.
Belgium squad in full: Thibaut Courtois (Real Madrid), Hendrik Van Crombrugge (Anderlecht), Simon Mignolet (Club Brugge), Matz Sels (Strasbourg); Toby Alderweireld (Tottenham), Dedryck Boyata (Hertha Berlin), Elias Cobbaut (Anderlecht), Jason Denayer (Lyon), Brandon Mechele (Club Brugge), Thomas Vermaelen (Vissel Kobe); Yannick Carrasco (Dalian Yifang), Timothy Castagne (Atalanta), Nacer Chadli (Anderlecht), Kevin De Bruyne (Manchester City), Leander Dendoncker (Wolves), Thorgan Hazard (Borussia Dortmund), Dennis Praet (Leicester City), Youri Tielemans (Leicester City), Hans Vanaken (Club Brugge), Axel Witsel (Borussia Dortmund); Michy Batshuayi (Chelsea), Christian Benteke (Crystal Palace), Eden Hazard (Real Madrid), Maxime Lestienne (Standard Liege), Romelu Lukaku (Inter), Dries Mertens (Napoli), Divock Origi (Liverpool), Leandro Trossard (Brighton and Hove Albion), Yari Verschaeren (Anderlecht).