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Sickle cell disease (SCD) pain is associated with colder temperatures and touch and described as "cold," "hot," and "shooting" suggesting hypersensitivity to tactile stimuli. Sickle mice exhibit hypersensitivity to thermal (cold, heat) and mechanical stimuli compared to controls. It is unknown whether humans experience this same hypersensitivity. Thus, we quantified thermal and mechanical sensitivity differences between patients with SCD and controls. Our primary hypothesis was that patients with SCD will exhibit hypersensitivity to thermal and mechanical stimuli compared to race-matched controls. Our secondary hypothesis was this hypersensitivity will be associated with older and female subjects, and with frequent pain and hemolysis in patients with SCD. A total of 55 patients and 57 controls ≥7 years completed quantitative sensory testing. Patients with SCD detected the sensation of cold and warm temperatures sooner as seen in their significantly lower median cold and heat detection thresholds [29.5°C vs. 28.6°C, P = 0.012 and 34.5°C vs. 35.3°C, P = 0.02] and experienced cold and heat pain sooner as seen in their significantly lower median cold and heat pain thresholds [21.1°C vs. 14.8°C, P = 0.01 and 42.7°C vs. 45.2°C, P = 0.04]. We found no mechanical threshold differences. Older age was associated with lower cold, heat, and mechanical pain thresholds in both groups. No association with pain, gender, or hemolysis was found. Patients with SCD exhibit hypersensitivity to thermal stimuli suggesting peripheral or central sensitization may exist and could contribute to SCD pain.