Novak Djokovic experienced a significant setback at the US Open on Friday, falling to Alexei Popyrin in a 6-4, 6-4, 2-6, 6-4 defeat in the third round. This loss halted the Serbian's pursuit of his 25th Grand Slam title. Djokovic, the defending champion who had recently secured an Olympic gold medal after a tough battle, appeared off-pace against the dynamic Popyrin. The latter secured the most notable victory of his career, advancing to the round of 16 in a major tournament for the first time. Despite having five break point chances in the initial set, Djokovic couldn't capitalize on any, whereas Popyrin seized his first opportunity to lead 5-4 and then claimed the set. Popyrin further asserted his dominance in the second set by breaking Djokovic's serve when the latter's forehand volley missed wide, giving Popyrin a 3-2 lead. He then solidified his control with a well-executed serve and volley to win the second set. Djokovic briefly revived his chances in the third set, breaking Popyrin's serve with a forehand that his opponent couldn't return, but this resurgence was short-lived. Popyrin roared in triumph after delivering a powerful forehand winner to break serve and take a 3-2 lead in the fourth set. The match concluded with Djokovic's forehand going long on match point.