Infection with hepatitis B or C viruses is still one of the most dreaded infectious diseases worldwide. Health education and screening, particularly among vulnerable groups, are the most cost-effective interventions that can be provided in developing countries. Facility and community-based provision, of effective strategic health education and counseling, are dependent on better understanding of the factors that may be associated with the level of knowledge on hepatitis. One of such groups is men who sleep with men (MSM) or homosexuals, who are at high risk of hepatitis infection through unprotected anal intercourse. This study was therefore aimed at assessing the knowledge of hepatitis infection among MSM in Calabar, a metropolitan city in the oil-rich Niger-Delta region of Nigeria. Cross-sectional study design was utilized. The snow-ball sampling method was used to recruit subjects, with self-administration of structured questionnaires. Questionnaire assessed awareness, causes, sources, consequence, and prevention of hepatitis infection. Knowledge scores were obtained for each subject. Chi-square was used to assess factors associated with knowledge, with p-value fixed at 0.05. Sixty-nine (69) consenting subjects were surveyed, with mean age of 22.5 ± 3.2 years, ranging from 16 to 31 years. Mean knowledge percentage score was 43.5 ± 32.0, ranging from 0% to 100%. Age group, occupation, and other sociodemographic characteristics were not significantly associated with the knowledge of hepatitis infection. There is inadequate knowledge of hepatitis infection among MSM in the study area. This inadequacy appears worse among receivers, who are even at higher risk of sexually transmitted infections compared with inserters. These findings have implications for control of viral hepatitis in sub-Saharan Africa.