Background: The management of sickle cell involves a strong emphasis on self-care throughout life. In this disease, the patient's ability to perform behaviors that help relieve the experience of pain enables the long-term adaptation of the patient to pain. Objective: The present study was conducted to describe the self-management of pain in Iranian patients with sickle cell anemia. Materials and Methods: The present qualitative content analysis was conducted on 19 purposively-selected participants. Data were collected through unstructured interviews and analyzed using the steps proposed by Graneheim and Lundman (2004). Results: Five main themes emerged from the analysis of the data, including adherence to the medication regimen, adherence to a particular lifestyle, having social support, receiving training from the health personnel, and adaptation efforts. Conclusion: The patients considered the regular use of the prescribed medications and adherence to their particular lifestyle as a means for managing pain attacks. They also benefited from social support, the training provided by the health personnel, and relevant adaptive mechanisms.