Purpose: The present investigation examined the physiological and performance effects of lower-body compression garments (LBCG) during a one-hour cycling timetrial in well-trained cyclists. Methods: Twelve well-trained male cyclists ([mean ± SD] age: 20.5 ± 3.6 years; height: 177.5 ± 4.9 cm; body mass: 70.5 ± 7.5 kg; V_O2max: 55.2 ± 6.8 mL·kg^-1·min^-1) volunteered for the study. Each subject completed two randomly ordered stepwise incremental tests and two randomly ordered one-hour time trials (1HTT) wearing either full-length SportSkins Classic LBCG or underwear briefs (control). Blood lactate concentration ([BLa^-]), heart rate (HR), oxygen consumption (VO2) and muscle oxygenation (mOxy) were recorded throughout each test. Indicators of cycling endurance performance were anaerobic threshold (AnT) and V_O2max values from the incremental test, and mean power (W), peak power (W), and total work (kJ) from the 1HTT. Magnitude-based inferences were used to determine if LBCG demonstrated any performance and/or physiological benefits. Results: A likely practically significant increase (86%:12%:2%; η² = 0.6) in power output at AnT was observed in the LBCG condition (CONT: 245.9 ± 55.7 W; LBCG: 259.8 ± 44.6 W). Further, a possible practically significant improvement (78%:19%:3%; η² = 0.6) was reported in muscle oxygenation economy (W·%mOxy^-1) across the 1HTT (mOxy: CONT: 52.2 ± 12.2%; LBCG: 57.3 ± 8.2%). Conclusions: The present results demonstrated limited physiological benefits and no performance enhancement through wearing LBCG during a cycling time trial.