Purpose: To examine the effects of acute caffeine supplementation on physical performance during fitness testing and activity during simulated games in basketball players. Methods: A double-blind, counterbalanced, randomized, crossover study design was followed. A total of 14 professional male basketball players ingested a placebo (sucrose) and caffeine (6 mg·kg−1 of body mass) in liquid form prior to completing 2 separate testing sessions. Each testing session involved completion of a standardized 15-minute warm-up followed by various fitness tests including 20-m sprints, countermovement jumps, Lane Agility Drill trials, and a repeated-sprint-ability test. Following a 20-minute recovery, players completed 3 × 7-minute 5-vs-5 simulated periods of full-court basketball games, each separated by 2 minutes of recovery. Local positioning system technology was used to measure player activity during games. Players completed a side-effects questionnaire 12 to 14 hours after testing. Results: Players experienced significant (P < .05), moderate–very large (effect size = −2.19 to 0.89) improvements in 20-m sprint, countermovement jump, Lane Agility Drill, and repeated-sprint-ability performance with caffeine supplementation. However, external workloads completed during simulated games demonstrated nonsignificant, trivial–small (effect size = −0.23 to 0.12) changes between conditions. In addition, players reported greater (P < .05) insomnia and urine output after caffeine ingestion. Conclusions: Acute caffeine supplementation could be effective to improve physical performance during tests stressing fitness elements important in basketball. However, acute caffeine supplementation appears to exert no meaningful effects on the activity completed during simulated basketball games and may promote sleep disturbances and exert a diuretic effect when taken at 6 mg·kg−1 of body mass in professional players.