Introduction: Sickle cell disease (SCD) patients are at high risk of experiencing poor outcomes, which can develop organ damage. After a definitive diagnosis has been made, the parents should start a comprehensive educational program about their child's condition. This program should include practical information about the various complications and preventive measures of the sickle cell crisis. The role of the caregiver in the prevention of sickle cell crisis focuses on avoiding demanding physical activities, smoking, and environments with low oxygen pressure, such as non-pressurized airplane flights and high altitudes as well as avoiding exposure to the sun and enough hydration for a sickler child. The study aimed to assess the knowledge and attitude of caregivers toward the preventive measures of the sickle cell crisis. Methods: A descriptive cross-sectional study design was conducted in the Sickle cell referral clinic, Dr. Gaafar Ibnauf Paediatric Hospital, Khartoum, Sudan, with a random sample of 286 caregivers who attended the referral clinic during the study period between September and December 2021. Data were collected using a pre-structured investigator-filled questionnaire. Proportion and binomial tests were used to investigate the statistical significance of the knowledge and attitude of caregivers toward the preventive measures of sickle cell crisis. Results: The vast majority of participants were female from the second class with intermediate educational levels. The study findings showed that 59% of caregivers have satisfactory knowledge while 41% of caregivers have unsatisfactory knowledge about the preventive measures for sickle cell crisis. Negative attitude toward the preventive measures of sickle cell crisis have been observed in 85% of the studied group. Keywords: Knowledge, Attitude, Caregivers, Preventive measures, Sickle cell, crisis.