Former US Open champion Medvedev, who finished runner-up at Melbourne Park in 2021 and 2022, ground out a 7-6(4), 2-6, 6-3, 5-7, 6-4 victory over Hubert Hurkacz after nearly four hours in searing heat on Rod Laver Arena to reach the semi-finals.
He had laboured to a similar five-set victory over Emil Ruusuvuori in a contest that finished at almost 4 a.m. local time last week, but felt similarly worn out despite cooler conditions to play in.
"After every match I'm in the locker room I'm destroyed," Medvedev told reporters. "But then we do a good job. One day off is probably enough to feel good the next day.
"So far, so good in the beginning of the matches and that's what matters. Then try to win and if you're dead after, doesn't matter because you have a day off."
Medvedev, who will face either second seed Carlos Alcaraz or sixth seed Alexander Zverev for spot in the title clash, said he had "no idea" why he felt so fatigued.
"Maybe I should dig into it more, because we try hard with my team to put myself at the 100% of my abilities, and I think we do it," Medvedev added.
"For me, the question is, is it maybe something where you have to work, like from 14 till 20 really hard on your aerobic, physical, whatever?
"Sometimes I see some guys, Hubi's one of them, and I see them play five-set matches, 7-6 in the fifth, they seem fine in the locker room. I'm, like, 'wow. Did he look good? Right'. That's what I'm saying."
Medvedev wondered if it was all down to his metabolism or genetics, but said he always worked with his team to be ready for the next challenge.
However, he pointed to a Davis Cup match against Novak Djokovic in 2017 where he retired in the fourth set after starting to suffer cramps as early as the second.
"Probably everyone works hard, but I know what I started doing with my team since I was 22, 23 when I decided to be more professional... if I didn't, today after the third set I'm done," Medvedev said.
"I'm trying my best. I'd love to be someone who's not really tired, doesn't care about the heat, but that's not me. But I try to win as I can."
