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For many patients with sickle cell disease (SCD), jaundice is a significant clinical disease manifestation that impacts on patient well-being. We report a case of a patient with SCD and chronic jaundice treated with voxelotor (GBT440), a novel small molecule hemoglobin oxygen affinity modulator and potential disease-modifying therapy for SCD. The case patient is a 27-year-old Black male with a long history of SCD with clinical jaundice and scleral icterus. After starting voxelotor, the patient reported that his jaundice cleared within one week, and that he felt much better with more energy, and was relieved after his eyes cleared. Voxelotor reduced bilirubin and unconjugated bilirubin (by up to 76%), and hemoglobin improved from 9.9 g/dL at baseline to 11.1 g/dL at 90 days. Jaundice impacts many adults with SCD, significantly impacting self-image. Voxelotor treatment reduced bilirubin levels and improved jaundice, resulting in an improved sense of well-being in our case patient., Competing Interests: Conflict of interest: Paul Telfer: ApoPharma and Terumo (honoraria); Bluebird Bio, Novartis, and GBT (consultancy); Kyora Kirin and Mundi Pharma (research funding); Pfizer (other, participation in EDMC). Irene Agodoa, Marzena Jurek, Margaret Tonda, and Josh Lehrer-Graiwer: GBT (employment and equity ownership); Kathleen M. Fox and Laurie Burke: GBT. (consultancy); Timothy Mant: IQVIA (employment and research funding); NIHR (research funding).