OBJECTIVES: Early tissue injury and recurrent pain in sickle cell disease (SCD) may alter pain and sensory processing. In this study, we evaluate thermal pain and sensory processing for 27 children aged 10.3 to 18.3 years with SCD and 28 African-American control patients. MATERIALS AND METHODS: Outcome measures included heat and cold detection thresholds, heat and cold pain thresholds, and thermal perceptual sensitization at the volar surface of the dominant forearm and thenar eminence of the nondominant hand. RESULTS: Children with SCD were less sensitive to heat detection (P=0.006) and cold detection (P=0.015) stimuli at the thenar eminence compared with controls. At the forearm, no difference was found between groups for cold (P=0.58) or heat (P=0.07) detection thresholds. Children with SCD had increased sensitivity to cold pain at the forearm (P=0.03) compared with controls, but not when measured at the thenar eminence (P=0.084). There was no evidence that children with SCD had altered heat pain thresholds compared with controls. There was no difference between groups for perceptual sensitization at the thenar eminence (41% vs. 39%) (χ=0.15, P>0.1) or at the forearm (30% vs. 36%) (χ=0.23, P>0.5). DISCUSSION: Three of ten quantitative sensory tests were found to differ between groups. These results suggest that SCD may influence pain and sensory processing in children, but our interpretation is necessarily cautious. Due to the small differences in measures found between groups, further investigation is required to confirm our findings. If confirmed, the development of population-specific reference standards for quantitative sensory testing may emerge as a useful clinical tool for pain physicians in identifying and quantifying pain and sensory processing in children with SCD.