Somatic symptoms have been extensively studied in primary care, but infrequently in diseases causing pain in multiple sites. We therefore examined the impact of somatic symptom burden (SSB) on pain, depression, anxiety, health-care utilization, and quality-of-life in adults with sickle cell disease (SCD). Subjects were 230 adults in the prospective Pain in Sickle Cell Epidemiology Study (PiSCES). Baseline data included demographics, genotype, Patient Health Questionnaire (PHQ), and SF-36 health-related quality of life (HRQOL). In daily diaries for 6 months, patients recorded SCD pain and SCD health-care utilization. To exclude common SCD pain sites, we abridged the PHQ's 15 somatic symptoms to 11 (PHQscd). We divided subjects into two groups: PHQscd≥11 (high SSB), and PHQscd<11 (low SSB). High SSB occurred in 18.3% of subjects and was more frequent in women than men (24.6% vs. 9.1%, p=0.0033). Sixty percent of subjects with anxiety and 37.5% of those with depression had comorbid high SSB. Percentage of pain days not in crisis pain was significantly higher in somatizers, but crisis pain did not differ between groups. The high SSB group's hospitalization, scheduled doctor visits, and overall utilization, particularly on non-crisis days were significantly higher than the low SSB group's (p values < 0.05). All SF-36 subscales were significantly negatively correlated with PHQscd (p<0.0001). Even after excluding common SCD pain complaints, high somatic symptom burden was 1.5 to 2 times more prevalent in SCD patients than in primary care. High SSB in SCD predicts more non-crisis pain and healthcare utilization for pain, and is associated with depression, anxiety, and poorer HRQOL.