Per ESPN FC's Dermot Corrigan, manager Zinedine Zidane is treating the Germany international with caution after he suffered a rib complaint following Wednesday's 1-0 defeat to Real Betis:
As Corrigan further noted, he is far from the only player absent from the match:
According to Sport, Kroos "had similar issues last season," and his injury means Real now have just 18 senior players to call upon for the trip to Alaves.
The blow comes amid a fairly disastrous start to Los Blancos' campaign in La Liga, with Real already seven points behind Barcelona after winning just two of their five matches.
With Mateo Kovacic also out, Zidane may opt to field Isco alongside Casemiro and Luka Modric in midfield.
The Spaniard has been in superlative form of late, but having Kroos' metronomic passing and control in the centre will be missed.
Fortunately for Los Blancos, their weekend opponents have failed to register a single point or even a goal this term, but with Borussia Dortmund looming in the Champions League on Tuesday, it's far from ideal to potentially be without another key player.