Max Verstappen took top spot in final practice for the Miami Grand Prix as Lewis Hamilton finished only 13th.
Verstappen clocked the best time in Saturday’s running, and the world champion will head into qualifying at 4pm (9pm BST) as the favourite to secure pole position.
Charles Leclerc finished second for Ferrari – four tenths slower than Verstappen – with Sergio Perez, six points behind Red Bull team-mate Verstappen in the driver standings, third.
Ferrari’s Carlos Sainz finished fourth. Hamilton’s team-mate George Russell was 10th.
Hamilton has described Mercedes’ form at the first of three rounds to be staged in the United States as a “kick in the guts”.
He heads into Sunday’s race 45 points behind championship leader Verstappen after just four rounds of the season.
The British driver’s Mercedes team have endured a turbulent campaign. Hamilton finished second in Australia at the beginning of last month to raise hope of a Mercedes fightback.
But the 38-year-old, whose contract with the Brackley team expires in just over six months, was a distant sixth in Azerbaijan last weekend.
And, despite an encouraging opening practice session on Friday, with Russell leading his team-mate in a Mercedes one-two, the Silver Arrows look poised for another troubling weekend.
Hamilton ended the concluding running before qualifying 1.1 seconds slower than Verstappen. Russell outpaced his team-mate by 0.1 sec.
Mercedes are due to introduce an upgrade at the next round in Imola in a fortnight’s time, but team principal Toto Wolff has already warned Hamilton that he will not have the speed to fight with Red Bull.
“We desperately need those upgrades, that is for sure. We have to keep our heads down for one more race and hopefully we will start a new path at the next race.”