The capital club - who sit third in the table, three points adrift of leaders and neighbours Atletico Madrid and two behind arch-rivals Barcelona - confirmed on Thursday that Ronaldo has suffered a thigh injury.
Although Real have put no timescale on their top scorer's return, reports suggest he will be sidelined for around two weeks - which would mean he will also miss next week's Copa del Rey final against Barca and the first leg of their UEFA Champions League semi-final.
Ronaldo, who has scored 45 goals in all competitions for Real this term, sat out both last weekend's 4-0 win over Real Sociedad and the Champions League last-eight second leg at Borussia Dortmund with a knee complaint.
A first-half brace from Marco Reus had Dortmund harbouring hopes of an improbable comeback following their 3-0 first-leg defeat in Spain, but Carlo Ancelotti's team held on to book a place in the last four alongside Atletico, Bayern Munich and Chelsea.
Following the game in Germany, Ancelotti indicated to Marca that Ronaldo would be ready to play against Almeria, but the FIFA Ballon d'Or holder's return has been delayed by another setback.
However, Real should still have far too much firepower for Francisco's 19th-placed side, who they beat 5-0 away back in November - with Ronaldo opening the scoring before being withdrawn due to a knock.
Nine unanswered goals against Rayo Vallecano and Sociedad have partially repaired the damage caused to Real's title charge by back-to-back defeats to Barca and Sevilla last month.
And like second-placed Barca - who visit Granada on Saturday - Ancelotti's men can apply pressure on pacesetters Atletico, as they play Getafe 24 hours after their rivals.
Such concerns are a world away from the issues Almeria face, although the battle to stay in La Liga is even more condensed that the scrap for title glory.
Basement boys Real Betis are somewhat cut adrift, eight points behind Francisco's team, but four points then cover 19th up to 15th.
The Almeria squad will doubtlessly pay close attention to Friday’s meeting between Osasuna and Real Valladolid, with those clubs sitting 16th and 17th respectively.
Next month's consecutive games against Betis and Granada are more likely to have a greater bearing on Almeria's fate than Saturday's daunting trip to the Bernabeu, where they were beaten 8-1 on their last Liga visit in May 2011.
The last of their three away league wins this term came at Betis in December, after which seven straight defeats on the road have followed.
