OBJECTIVES: Sickle cell vaso-occlusive crises (VOCs) are painful episodes experienced by patients with sickle cell disease (SCD) and triggered by multi-cell adhesion or cell clusters that block or reduce blood flow. This study aimed to explore the relationship between VOCs and work productivity in patients with SCD. METHODS: Patients with SCD completed questionnaires as part of an online study. VOC frequency and severity were assessed with the Adult Sickle Cell Quality of Life Measurement Information System (ASCQ-Me). Patients also answered questions regarding employment impacts and completed the Workplace Productivity and Activity Impairment: Specific Health Problem (WPAI-SHP), which assesses productivity over the past 7 days, including absenteeism (missed work), presenteeism (impairment at work), and overall productivity loss among employed patients (N=100), and activity impairment among both employed and non-employed patients (N=251). Patients were stratified according to the frequency of VOCs over the past 12 months (0-3 VOCs; ≥4 VOCs) and the severity of VOCs (ASCQ-Me pain severity score: ≥55; <55). Differences according to VOC frequency and severity were assessed for WPAI domains using Kruskal-Wallis tests. RESULTS: Fifty-eight percent of patients reported that SCD negatively impacted their employment status; 73% of patients with ≥4 VOCs in the past year reported negative impacts compared to 45% of patients with 0-3 VOCs. Patients with more frequent VOCs also reported greater absenteeism, overall productivity loss, and activity impairment than patients with less frequent VOCs (p<.05 for all). Presenteeism did not differ according to VOC frequency (p=.132). Similar patterns were observed when examining reports of negative work impacts and WPAI scores according to VOC severity (p<.05 for all domains except presenteeism). CONCLUSIONS: VOC frequency and severity are both associated with work productivity; patients with more frequent or severe VOCs missed more work in the week preceding survey administration than patients with less frequent or severe VOCs.