Iniesta is a doubt for the second leg of the uefa Champions League last-16 tie with Chelsea on 15 March (AEDT) after sustaining a hamstring problem in the 1-0 win over Atletico Madrid.
The 33 year-old attempted to play through the injury before he eventually made way for Andre Gomes in the 36th minute.
With Philippe Coutinho ineligible for European competition, Chelsea's visit to Camp Nou could require Barca to repair two key components from the team that started on Monday.
"He cannot be matched, like Messi. You cannot replace a unique player like him," Valverde said. "We are going to wait to see the scan of the injury. It looked like a muscle tear, but we will hope that it is not so serious.
"He knows how to manage himself. He was having a great game."
Iniesta's early withdrawal against second-placed Atleti was ultimately softened by a victory that improved Barca's lead in LaLiga to eight points with 11 matches remaining.
Lionel Messi netted the winner with a sublime first-half free-kick, his 600th career goal for club and country.
"There is no player like Messi in the world," Valverde said. "I do not know what would have happened if he was playing for Atletico. I don’t want to imagine it, either."