Murray and Lopez have been scheduled for the third match on the Hisense Arena, not before 03:30 GMT.
The Wimbledon champion did not drop a set in rounds one and two - only his third and fourth competitive matches since recovering from back surgery.
He boasts a 7-0 record against Lopez, but their last meeting was a close one.
"I had a tough match with him at the US Open on the hard courts two years ago where he played well," said the Scot.
"I think it was 7-6 in the fourth set on a very, very hot day."
The temperature has been the theme of the opening week in Melbourne, with highs of over 40C for four days in a row, but the arrival of cooler air is forecast to bring a sharp dip to around 23C on Saturday.
Lopez, the 26th seed, has also reached the last 32 without dropping a set, but the 32-year-old from Toledo, Spain, is relishing the prospect of a more comfortable playing environment.
"Hopefully it's going to be a little bit cooler and we're going to play in better conditions," he told BBC Sport.
Asked how he would go about ending his run of defeats against the British number one, Lopez added:
"It's tough to say what I really need to do to beat Andy.
"He's a great player. We played so many times and I never beat him. A couple of times I was close - the best match I played was at the US Open [in 2012] when I was really close, but I didn't get it.
"So I have to play the same but still a little bit better, because that was not enough."
The fact that Murray has only been involved in four competitive matches since September is not something that has instilled a greater confidence in Lopez.
"It's always tough for a player to get back after surgery, and it's tough for Andy because he hasn't played so many matches," said Lopez.
"I think it's obviously something that counts, but not a lot when he already won two matches here. He's going to be ready."
Murray, 26, is still feeling his way back into the highest level of tennis after his surgery but has shown flashes of his major-winning form in beating Go Soeda and Vincent Millot in Melbourne.
Lopez is a classier opponent, however, ranked 27th but the world number 15 just two years ago.
"He's got a great serve," said Murray. "He obviously comes to the net a bit and has a different game style to all of the guys nowadays.
"So that will, again, be another good test for me and naturally get tougher."
Saturday's night session will begin with defending champion Victoria Azarenka against Austrian Yvonne Meusburger at 08:00 GMT, followed by world number one Rafael Nadal against French 25th seed Gael Monfils.
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