The Repsol Honda rider, who locked up the season title in Japan two weeks ago, posted a best lap of 2min, 1.21secs on a dry track in the morning.
But gastroenteritis forced him to pull out of the afternoon session, when Malaysia's tropical rains left the track wet, putting the brakes on lap speeds.
Riders on Friday were getting acquainted with tweaked conditions including a surface repaving at the Sepang International Circuit ahead of Sunday's event.
Fellow Spaniard Maverick Vinales of Suzuki, who is now fourth in the world championship standings, was 0.268 seconds off Marquez's pace.
Britain's Scott Redding was third-fastest at a gap of 0.297 seconds.
Marquez has an unassailable 57-point lead in the championship standings but has vowed no let-up in the final two races, at Sepang and next month at Valencia.
"We?ll try here to push from the beginning again, but with a different result," Marquez had said before practice.
"I?d like to finish as a minimum," he said, a reference to his crashing out of the Australian Grand Prix last weekend.
"But hopefully I?ll get on the podium and fight for the victory."
Marquez's clinching of the title leaves Italian legend Valentino Rossi, a nine-time motorcycling world champion, trying to hold off his Movistar Yamaha teammate Jorge Lorenzo of Spain in the fight for second-place.
Rossi posted the fifth-fastest lap on Friday, 0.401 seconds behind Marquez.
Lorenzo, who won the world title last year, was only tenth-fastest on Friday, 0.803 seconds off Marquez's speed.
Sepang is among the trickiest tracks due to the tropical heat and frequent rain.
The track has been resurfaced and some of its banking modified.
Officials have said the re-surfacing will help hasten water run-off and improve tyre grip.
But riders will be working over the next two days to determine exactly how it will affect traction, speed and tyre wear, and whether the banking changes require modified approaches to key turns.
Just ahead of Rossi on Friday was Andrea Iannone, who is returning to competition in Sepang for the first time since he suffered a vertebrae fracture in a crash in early September.
Like Marquez, he sat out the afternoon session, saying he did not want to risk a tumble on the slick surface, according to Motorsport.com.
"I'm very happy because this morning I had a very good feeling from the beginning with the bike," he said.
"With my injury, I have pain, but I manage very well at the moment. This is very important for all the weekend."