The Colombian attacker could be out for around two months with a broken metatarsal, while the centre-back remains a doubt for the derby clash against Atletico Madrid
James was replaced midway through the first half of Wednesday night's Liga clash with Sevilla after taking a blow to his right foot. The Colombia international, who opened the scoring in the 2-1 win, was taken to hospital for further assessment, where it was confirmed his fifth metatarsal was broken. Early reports suggest he could be sidelined for around two months.
Ramos, meanwhile, came off just nine minutes in with a suspected hamstring problem.
Blancos boss Carlo Ancelotti will be desperately hoping that the defender's injury does not prove so serious, with the Liga leaders set to travel to the Vicente Calderon for a crunch clash with their city rivals.
Madrid will, at least, be buoyed by the return of star forward Cristiano Ronaldo, who sat out Madrid's meeting with Sevilla, as well as last weekend's 4-1 win over Real Sociedad, after picking up a two-game ban for his dismissal against Cordoba on January 24.
However, the prospect of losing James and Ramos will be of great concern to Ancelotti. James has stepped up to the mark in Ronaldo's absence, netting in both of the games the Portuguese missed through suspension. Furthermore, the loss of the Spain international would leave Madrid with just two fit centre-halves - Raphael Varane and Nacho Fernandez - given veteran defender Pepe is still sidelined through injury.
Los Blancos will also have to make do without full-back Marcelo, who picked up a booking against Sevilla, ruling him out of the derby due to a mandatory ban.