Chronic pain affects 50% of adults with sickle cell disease (SCD). Although inflammation is thought to contribute to the pathogenesis of chronic pain, no studies have examined the differences in circulating cytokines between patients with SCD with and without chronic pain. We performed an observational cohort study using blood and urine samples from adults with SCD with and without chronic pain at their usual state of health. We tested the hypothesis that, compared to those without chronic pain, those with chronic pain would have significantly higher baseline circulating proinflammatory cytokines. A total of 61 adults with SCD, 40 with chronic pain and 21 without chronic pain were tested. When SCD patients with chronic pain were compared to those without chronic pain, no significant differences in cytokine levels were noted. The variables most associated with the diagnosis of chronic pain in this population were opioid dose and subject age.