Media reports have said Nuno is unhappy with comments Negredo made about tactics but the Portuguese underlined on Monday that the decision not to include him was "purely sporting".
Negredo, 30, left Manchester City in the close season for a fee of just under 30 million euros (22 million pounds) but has yet to reproduce the form that earned him 21 caps, with his most recent appearance for his country coming in November 2013.
He last played for Valencia in the 3-1 La Liga defeat at Athletic Bilbao on Oct. 4 and was omitted for Saturday's 3-0 victory at home to Malaga.
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"All the decisions we take on the squad are based solely and exclusively on sporting issues," Nuno told a news conference ahead of the clash at the Mestalla.
"We draw up the roster seeking the best for the team and for the game plan. It's a long season, there are a lot of competitions and everyone will be important."
Nuno selected three forwards for Tuesday's game, Spain international Paco Alcacer, Rodrigo and Santi Mina.
Goals have been scarce for Valencia this term and they have scored only seven in eight La Liga games, eight fewer than at the same stage last season.
The Singapore-owned club are back in Europe's elite club competition after a two-year absence and are second in Group H after a 3-2 defeat at home to Zenit St Petersburg and a 1-0 triumph at Olympique Lyonnais.
"I have confidence in all the players in the squad and I try to give my best as a coach to get the best out of each of them," said Nuno.
(Writing by Iain Rogers, editing by Tony Jimenez)
