Background: Measles is a highly contagious acute viral disease; it remains among the top causes of death in young children globally. The purpose is to study the serology and clinical profile of measles in Southern Darfur State, Sudan.Methods: Cross-sectional laboratory-based study was conducted (2011)(2012)(2013)(2014)(2015) in six health zones in Southern Darfur State, Sudan. A total of 511 sera were obtained from measles patients during the surveillance, and the sera were screened for IgM antibodies using ELISA.Results: A 43.4% of cases was males, and 56.6% were females, the commonly affected age was 1-4 years in both sexes. The sero-prevalence of measles lab-confirmed cases was 48.5%, most cases were reported in Nyala and Rahad Elberdi health zones. The suspected measles cases were increased from February to June and decreased from July to December. Measles lab-confirmed cases were higher compared with Epi-linked and Measles compatible cases in different health zone. The characteristic of measles clinical symptoms was fever 100%, cough 100%, maculopapular rash 100%, running nose 22.1%, conjunctivitis 67.3%, arthritis 25.8%, and lymphadenopathy 6.7%. However, 25.0% of cases had severe measles complication, 98.2% were recovered during the hospitalization, and 1.8% resulted in death. A 21.3% of cases were vaccinated, and 48.53% had measles IgM positive antibody. The trend of measles shown clinically significant differences in gender (χ 2 =55.68, P<0.001), age year (χ 2 =48.83, P<0.001) and presences of measles IgM antibody in the serum (χ 2 =261.27, P<0.001). Conclusion:The study reported a high percentage of measles IgM antibody in Southern Darfur State.