Although demodicosis caused by Demodex folliculorum and Demodex brevis is widely seen throughout the world, the pathogenic mechanisms are not fully known. To the best of our knowledge, the effect of Demodex mites in patients with sickle cell anemia (SCA) is not known. SCA is a genetic disease characterized by abnormal hemoglobin production and suppression of the immune system. The aim of this study was to determine the prevalence and Demodex density in SCA patients and to compare with healthy subjects. The study included 70 patients diagnosed with SCA and control group of 50 healthy individuals. Samples were taken from cheeks, forehead, nose, and chin and were examined microscopically. Infestation of ≥5 mites/cm² was accepted as positive in the diagnosis. Demodex mite positivity was determined in 20 (28.6%) patients and none in subjects of the control group. In the SCA group, the mean number of mites was 26.10/cm². A statistically significant correlation was found between Demodex mite positivity and the number of SCA symptom attacks experienced by the patients within the last 1 yr (P ≤ 0.001). No significant relationship was determined between Demodex mite positivity and age or gender (P = 0.56 and P = 0.11, respectively). Demodex mites are seen more often in SCA patients who suffer from a compromised immune system, and the presence of Demodex mites could be a risk factor in the appearance of SCA symptom attacks.