The Manchester City man adds to the club's injury woes and could be a doubt for Saturday's match with Stoke City after injuring his thigh in training with his national squad.
A statement from the Spanish Football Federation (RFEF) confirmed the attacker's withdrawal from the match, which is to be played in Geneva.
"After the issues reported by the player David Jimenez Silva after this afternoon's training session, a scan took place and a light muscle injury was detected. For precaution and to avoid complications with this injury, Silva left the training camp," the statement read. "National coach Vicente del Bosque has decided not to call up anyone else to cover the absence."
The 27-year-old Silva's injury could add to City's already notable fitness issues, with club captain Vincent Kompany, right back Micah Richards and summer signing Martin Demichelis already on the treatment table.
A short statement on the club's official website confirmed the knock but played down its seriousness, calling it a "minor injury."
"The midfielder has a slight thigh problem, which is not thought to be serious, and will return to Manchester to receive treatment and assessment by MCFC medical staff," City declared.
Earlier on Monday, the RFEF announced that Real Madrid summer recruit Isco had withdrawn from the friendly after failing to recover from an ankle knock.