This time, Rafael Nadal could not summon the third-set magic he needed.

Coming off an epic three-hour duel Wednesday in his first match since the French Open final, Nadal fell to Lloyd Harris 6-4 1-6 6-4 on Thursday at the Citi Open.

After a short-lived maiden appearance at the Washington, D.C. tournament, the Spaniard will look ahead to Toronto and Cincinnati as he continues his preparations for the U.S. Open.

Harris, meanwhile, heads to a quarter-final matchup against veteran Kei Nishikori after recording the biggest win of his career.

Facing Nadal for the first time, the 24-year-old South African slammed 16 aces Thursday and saved four of six break points.

The 20-time grand slam winner, who battled a foot injury to outlast Jack Sock in his first match, did not have enough to answer the world number 50 on Thursday.

In addition to the top-seeded Nadal's defeat, second seed Felix Auger-Aliassime also went down Thursday, falling 6-3 6-4 to American wild card Jenson Brooksby.

With their exits, the tournament is now without its top four seeds.

That leaves fifth seed Jannik Sinner as the top player remaining after he defeated Sebastian Korda 7-6 (7-3) 7-6 (7-3).

Nishikori advanced by downing seventh seed Cameron Norrie 3-6 6-3 6-3, while John Millman knocked out eighth seed Reilly Opelka 6-3 7-6 (7-4).

Among unseeded players, Denis Kudla defeated the red-hot Brandon Nakashima 3-6 7-6 (7-3) 6-4, while Steve Johnston eased past Ricardas Berankis 6-2 6-1 and Mackenzie McDonald beat Illya Ivashka 6-4 6-4.

In addition to Harris-Nishikori, Kudla will face McDonald in the other quarter-final in the top half of the draw, while Sinner meets Johnson and Millman takes on Brooksby in the bottom half.