Jan Vertonghen has been left out of the latest Belgium squad due to a hamstring injury and coach Roberto Martinez does not expect him to be fit in time for the next international break in mid-November.
The 31-year-old was forced off at half-time in Tottenham's 2-0 win at Huddersfield Town last Saturday and subsequently missed the 4-2 Champions League defeat to Barcelona.
Ahead of Barca's visit, Spurs manager Mauricio Pochettino said the club were assessing Vertonghen's condition and refused to outline a timeframe for his return.
But Martinez has had to leave him out of Belgium's squad and does not think he will be able to feature next month in the Nations League against Switzerland and Iceland either.
"Jan Vertonghen may miss the next two international camps, so also those games in November," Martinez told reporters on Friday. "It's bad news."
Nevertheless, Martinez is confident in Jason Denayer to step up after coming through a turbulent period in his career.
"Jason was going through a difficult time as a footballer," he said. "I think he learned a lot at Sunderland and Galatasaray.
"His hard work in these teams is now paying off, certainly now that he plays in Lyon and the Champions League."
Leander Dendoncker is the only fit player from Belgium's World Cup squad who has been overlooked for the upcoming games with Switzerland and Netherlands, and Martinez has told the Wolves midfielder he needs to be playing if he is going to be considered for selection.
"Leander has the qualities, he is part of our plans, but it is difficult to get to the national team if you do not play at your club," Martinez added. "He can now try to become important at his club."
Kevin De Bruyne, Christian Benteke, Adnan Januzaj and Mousa Dembele all miss out through injury, while Christian Kabasele and Dennis Praet join Denayer in returning and Brandon Mechele of Club Brugge gets his first call-up.
Belgium squad in full:
Thibaut Courtois (Real Madrid), Simon Mignolet (Liverpool), Koen Casteels (Wolfsburg), Matz Sels (Strasbourg); Toby Alderweireld (Tottenham), Vincent Kompany (Manchester City), Thomas Vermaelen (Barcelona), Dedryck Boyata (Celtic), Christian Kabasele (Watford), Jason Denayer (Lyon), Brandon Mechele (Club Brugge); Axel Witsel (Borussia Dortmund), Marouane Fellaini (Manchester United), Youri Tielemans (Monaco), Nacer Chadli (Monaco), Thomas Meunier (Paris Saint-Germain), Dennis Praet (Sampdoria), Hans Vanaken (Club Brugge), Yannick Carrasco (Dalian Yifang), Timothy Castagne (Atalanta); Romelu Lukaku (Manchester United), Michy Batshuayi (Valencia), Dries Mertens (Napoli), Eden Hazard (Chelsea), Thorgan Hazard (Borussia Monchengladbach), Leandro Trossard (Genk).