Watch the Australian Open live on Eurosport and Eurosport app
But he looked back to his best in the next round, dropping just six games as he defeated Mikael Ymer.
Nadal is yet to drop a set through the opening four rounds of the tournament, but Tsitsipas will have a longer rest due to Berrettini’s withdrawal.
For the Spaniard, he’s looking to win his first Australian Open title since 2009 – which will also give him the out-right men’s record for all-time Grand Slam wins.
He’s reached the final on four separate occasions since then, with his last coming in 2019 when Novak Djokovic defeated him in straight sets.