Carl Jenkinson, who is ineligible for Sunday’s Premier League opener against Arsenal, and Kevin Nolan are the only recognised first-team players who have travelled to Bucharest.
The home side Astra are expected to include former West Bromwich Albion midfielder Filipe Texeira in their starting line-up.
“It’s a different squad front the first game, but that was always the plan,” said Bilic.
“We were always going to play the first leg with the best team. But it was always part of our plan, because of the start of the Premier League on Sunday – which is the priority – that we would come here with a strong team – but a team where some players have stayed at home.”
“It would be very difficult to play here and then start at the Emirates on Sunday.
Bilic believes his young squad, consisting of Diego Poyet and new signing Manuel Lanzini, can still came away with a result that will see them secure a Europa League qualification play-off place.
“We weren’t happy with the result in the first leg, particularly after going 2-0 up after 55 minutes,” Bilic added.
“But this is a good game for us. It’s a European game and we are very respectful of this competition. Can we still win? Of course, why are we here otherwise?”
The match kicks off at Stadionul Marin Anastasovici at 19.00 BST.