Andoni Iraola said Joe Gomez's injury in Liverpool's friendly win against Sunderland was the "worst news" at the start of his reign.
Iraola was taking charge of his first match since arriving from Bournemouth in the close season to replace the sacked Arne Slot.
The Spaniard watched as goals from Kieran Morrison, Dominik Szoboszlai, Federico Chiesa and Lewis Koumas gave Liverpool a 4-2 victory on Saturday in the opener of their United States tour in Nashville.
But Gomez, who started the game as centre-back and captained Liverpool, was forced off in the eighth minute.
Gomez's premature exit added to Iraola's defensive issues, with new signing Jeremy Jacquet still being eased back after his own fitness problems and Giovanni Leoni recovering following a long-term absence.
Iraola said earlier this week that his squad is "very thin" defensively.
"Probably the worst news has been straight away the injury of Joe," Iraola said.
"We were happy because we were kind of going through all the training without losing any player. Unluckily for us, straight away we've lost Joe.
"With Jeremy, we decided to take it easy with him. He has been a lot of months without playing with a shoulder injury.
"So, I think we are going to take it easy with him. He will play probably the last game of this US tour and he will have time to have minutes."
Despite the injury woes, Iraola hopes the win will give Liverpool a platform to improve when they meet Wrexham in New York and Leeds in Chicago.
"A lot of things to correct, obviously, it's the first day. You could feel the heavy legs, the players have been training," he said.
"So, we lacked some freshness. But it will give us a good starting point to improve things."
Virgil van Dijk has been given extra time off following the Netherlands' World Cup campaign.
But Iraola confirmed that Alexander Isak, Florian Wirtz and Ryan Gravenberch are in Chicago after their post-World Cup breaks and will soon rejoin the squad.