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Cutaneous ulceration from sickle cell disease negatively impacts quality of life. Topical sodium nitrite has previously been shown to reduce the size of sickle leg ulcers. This study examined how topical sodium nitrite impacted the quality of life scores in patients with sickle leg ulcers.We prospectively collected data in patients enrolled in a leg ulcer study (n = 17) or an allogeneic hematopoietic cell transplant study (nonulcer group, n = 15). Both groups completed a pretreatment Short Form-36 questionnaire; the ulcer group completed a second questionnaire after 4 weeks of topical sodium nitrite applications. Data were analyzed by age, sex, >50% area improvement postintervention, and sickle-related complications (vaso-occlusive crises, pulmonary hypertension, or avascular necrosis). Physical and mental component summary scores were analyzed with Student t test.Physical summary scores were lower than mental summary scores in all groups, indicating leg ulcers among other sickle related complications negatively impacted physical quality of life measures. After sodium nitrite use, physical summary scores improved in the leg ulcer group (34.5 ± 9.4 to 39 ± 10.3, P = .03), and mental summary scores improved more in ulcerated patients ≤35 years old (40.7 ± 6.9 to 51.7 ± 9.7, P = .01).Brief topical sodium nitrite has the potential to improve quality of life, especially in younger individuals. Longer treatment duration and randomized-controlled trials are needed to confirm the efficacy of this topical therapy.