Background: Community Health Workers (CHWs) have played a key role in the holistic care of sickle cell disease (SCD) in the developed world. However, in Nigeria and other African countries which harbour the largest burden of SCD globally, the poor involvement of CHWs in the care of individuals with the disease may be related to their knowledge about the disease.   Objective: To assess the adequacy of knowledge or otherwise of CHWs-in-training (students of School of Health Technology) in SCD identification, screening and crises prevention. Methods: This cross-sectional study involved 600 students of the College of Health Technology, Ilesa, southwest Nigeria. A pre-tested self-administered forty-point questionnaire was used to assess information on what SCD is and how it is transmitted (6 questions); major clinical presentations (8 questions); ideal timing for diagnosis (7 questions); common methods of crisis prevention (7 questions); basic counselling of individuals with the disease (6 questions); and knowledge on the relevance of record keeping, home visit, immunisation and prompt referral in SCD care (6 questions). Results: Only 239 (39.8%) had good knowledge of SCD in the assessed domains. Knowledge on crisis prevention including roles of record keeping, home visits, immunisation and prompt referral in SCD care was particularly poor. Age group, gender and course of study were not significantly associated with the overall knowledge of the disease. Conclusion: The overall knowledge of Health Technologists-in-training in Nigeria on SCD is poor. Focused and comprehensive modules on SCD should be incorporated into the training curriculum of students in the Colleges of Health Technology in Nigeria.