Valencia earned a convincing 3-1 victory over Monaco on Wednesday to leave them on the verge of qualifying for the Champions League group stage.
Nicolas Otamendi was omitted from Los Che's squad for the match, with the player understood to be nearing a €40m switch to Manchester City, while Aymen Abdennour, who also continues to be the subject of links with his own move away, was also absent.
Nuno Santo, meanwhile, opted for Matthew Ryan between the sticks, Antonio Barragan and Jose Luis Gaya in the full-back positions and Ruben Vezo replacing Otamendi in partnering Shkodran Mustafi at centre-back.
Further up the pitch, Enzo Perez shielded Dani Parejo and Rodrigo de Paul in the middle of the park, while Rodrigo and Sofiane Feghouli supported lone striker Paco Alcacer.
For Monaco, on the other hand, Layvin Kurzawa and Stephan El Shaarawy were both missing from the starting XI, although there were places for ex-La Liga loanees Mario Pasalic and Ivan Cavaleiro
Inside just four minutes, Valencia took the lead through Rodrigo, who connected with Feghouli's header at the far post, sliding into an empty net.
Los Che would dominate the next half-hour, Alcacer notably flinging himself onto the end of Gaya's cross-field pass but failing to toe-poke past Danijel Subasic.
However, Monaco finished the first half strongest and came within a whisker of equalising as Bernardo Silva saw his angled strike tipped onto the post by Ryan.
The Principality side also had a goal chalked off for offside, rightly so as Anthony Martial was flagged marginally ahead of his marker and last man Shkodran Mustafi prior to netting a rebound.
Their positive end to the half trickled into the opening stages of the restart as Martial's lightning wing play resulted in a low cross for Pasalic to slam home on the rebound.
However, the inspired introduction of Pablo Piatti for the ineffective De Paul signalled the pendulum swinging back to Valencia, captain Parejo firing past Subasic in the box, albeit aided by a deflection from Cavaleiro.
Valencia then wrapped up a comprehensive win ahead of the return leg at Stade Louis II, when Feghouli took advantage of a loose ball from a corner and drove a shot into the bottom-left corner of the Croat's net.
The Ligue 1 outfit could have left Spain with a vital, second away goal before full-time, but Ryan proved just why he was signed as Diego Alves' replacement after he somehow pushed out Martial's header from point-blank range.
Valencia 3-1 Monaco
Rodrigo 4, Parejo 59, Feghouli 86 (V) Pasalic 49 (M)
Valencia: Ryan; Barragan, Mustafi, Vezo, Gaya; Parejo, Perez (Negredo 76), De Paul (Piatti 56); Feghouli, Alcacer (Fuego 56), Rodrigo
Monaco: Subasic; Raggi, Carvalho, Wallace; Fabinho, Toulalan, Pasalic (Bahlouli 76), Silva (El Shaarawy 78), Elderson; Martial, Cavaleiro (Dirar 63)
Referee: Clattenburg [ENG]
