Otamendi, 27, a fierce tackler who is also strong in the air, is poised to join Manchester City for a fee of 45 million euros (31.7 million pounds), Spanish media reported on Tuesday.
Nuno did not confirm a deal had been reached but said an announcement would come soon.
"There is nothing more important than the Monaco match," the Portuguese told a news conference.
"We have been preparing the game for days without the option of Otamendi. The players are exclusively focussed on the opponent."
Valencia, the 2000 and 2001 Champions League runners-up, qualified for the playoffs thanks to a fourth-place finish in La Liga last season and are hoping to secure a lucrative spot in the group stage for the first time in three years.
Singapore billionaire Peter Lim bought a majority stake in the club in 2014 and is hoping his investment will help them return to the summit of the game in Spain and Europe.
In their only previous meeting with Monaco, in the 1980-81 European Cup Winners' Cup first round, holders Valencia beat the principality club 5-3 on aggregate.
(Reporting by Iain Rogers, editing by Tony Jimenez)
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