Objective: To determine whether particular semen characteristics in various clinical diagnoses of infertility are associated with high oxidative stress and whether any group of infertile men is more likely to have high seminal oxidative stress. Reactive oxygen species (ROS) play an important role in sperm physiological functions, but elevated levels of ROS or oxidative stress are related to male infertility. Design: Measurement of sperm concentration, motility, morphology, seminal ROS, and total antioxidant capacity (TAC) in patients seeking infertility treatment and controls. Setting: Male infertility clinic of a tertiary care center. Patient(s): One hundred sixty-seven infertile patients and 19 controls. Intervention(s): None. Main Outcome Measure(s): Semen characteristics, seminal ROS, and TAC in samples from patients with various clinical diagnoses and controls. Result(s): Fifteen patients (9.0%) were Endtz positive and 152 (91.0%) Endtz negative. Sperm concentration, motility, and morphology were significantly reduced in all groups compared with the controls ( P = .02), except in varicocele associated with infection group. Mean (±SD) ROS levels in patient groups ranged from 2.2 ± 0.13 to 3.2 ± 0.35, significantly higher than controls (1.3 ± 0.3; P<.005). Patient groups had a significantly lower mean (±SD) TAC from 1014.75 ± 79.22 to 1173.05 ± 58.07 than controls (1653 ± 115.28, P<.001), except in the vasectomy reversal group (1532.02 ± 74.24). Sperm concentration was negatively correlated with ROS both overall and within all groups ( P≤.007), with the exception of idiopathic infertility. Conclusion(s): Irrespective of the clinical diagnosis and semen characteristics, the presence of seminal oxidative stress in infertile men suggests its role in the pathophysiology of infertility. Medical or surgical treatments for infertility in these men should include strategies to reduce oxidative stress.