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ObjectivesMindfulness-based stress reduction (MBSR) has been shown to improve mental health and reduce stress in a variety of adult populations. Here, we explore the effects of a school-based MBSR program for young urban males. Participants and methods In fall 2009, 7th and 8th graders at a small school for low-income urban boys were randomly assigned to 12-session programs of MBSR or health education (Healthy Topics—HT). Data were collected at baseline, post-program, and three-month follow-up on psychological functioning; sleep; and salivary cortisol, a physiologic measure of stress. Results Forty-one (22 MBSR and 19 HT) of the 42 eligible boys participated, of whom 95% were African American, with a mean age of 12.5 years. Following the programs, MBSR boys had less anxiety (p = 0.01), less rumination (p = 0.02), and showed a trend for less negative coping (p = 0.06) than HT boys. Comparing baseline with post-program, cortisol levels increased during the academic terms for HT participants at a trend level (p = 0.07) but remained constant for MBSR participants (p = 0.33). Conclusions In this study, MBSR participants showed less anxiety, improved coping, and a possible attenuation of cortisol response to academic stress, when compared with HT participants. These results suggest that MBSR improves psychological functioning among urban male youth.