Marcelino's men are in complete control of the tie and will be expected to wrap up victory on home soil.
Brendan Rodgers' Hoops will still harbour hopes of turning this tie on its head, but it would require a remarkable reversal of fortunes if Celtic are to progress - especiallyt given their poor away record in this competition.
A draw, of course, would see Marcelino's men safely through to the last 16. William Hill go 29/10 (3.90) that the match ends in stalemate.
Celtic must take the game to the Spanish side. Odsonne Edouard and Timothy Weah, second half substitutes in the first-leg, may start in Spain.
Valencia could name the same starting line-up as they look to cruise into the next round in a comfortable fashion.
Celtic defeated Rosenborg 1-0 in Trondheim in November in the group stage of this competition but that was Celtic's first win in 15 Europa League ties outside of Glasgow.
However, Celtic have scored in three of their last four Europa League ties away from home and William Hill go 17/20 (1.85) that there are goals at both ends when the Scots travel to Spain.
Despite that, the Hoops have scored more than once in just one of their last nine Europa League away matches so it is no surprise to see a chunky 3/1 (4.0) on Rodgers' side scoring more than a single goal.
Valencia will fancy their chances of recording another convincing victory and it is William Hil's 8/5 (2.60) on Marcelino's side to win by at least two goals when they play host to the Hoops that represents the best bet for punters here.