Goals from Denis Cheryshev and Ruben Sobrino secured Valencia a handy lead to take back to Mestalla after the first leg against Celtic.
Valencia took a huge step towards the last 16 of the Europa League with a 2-0 first-leg win at Celtic on Thursday.
The Spanish side dropped out of the Champions League after finishing behind Juventus and Manchester United but possessed the cutting edge required to damage Celtic's hopes of progressing in the competition.
Brendan Rodgers' men conceded for the first time in all competitions in 2019 as Denis Cheryshev and Ruben Sobrino netted either side of half-time to put Valencia in complete control of the tie.