Worldwide, soil transmitted helminthes (STH) infections are among the major disease of public health problem in tropical and subtropical countries [1]. In many developing countries; one of the most prevalent and most important helminthes are the blood flukes, schistosomes. Schistosomiasis is a chronic illness that can damage internal organs, seriously undermine the work capacity of rural workers and, in children, impair growth and cognitive development. It is caused by several species of which the most prevalent are S. mansoni, S. haematobium, and S. japonicum. It is estimated that 200 million people are already infected of which 180 million are Africans, fewer than 5% of whom are receiving treatment with 779 million peoples at risk. The large fresh water reservoirs associated with ecological changes are contributing for the increased prevalence of S. mansoni. The increased prevalence of S. mansoni infection results in the formation of periportal fibrosis. Though there are morbidities in different S. mansoni areas, disparities in the formation of periportal fibrosis have been observed in different corners of the world. The current study is focused in assessing the prevalence of S. mansoni, PPF and measurement of total serum antioxidant (TSA) in Schistosoma mansoni endemic and non-endemic areas to associate total serum antioxidants with infection intensity and periportal fibrosis of S. mansoni infection in Worke-mado. A community based cross sectional parasitological and schistosomal morbidity survey was conducted on 390 study subjects recruited by systematic sampling technique from the sampling frame in Worke-mado from January to May, 2013. A total of 390 study subjects and 30 controls were included in this study. An overall prevalence of intestinal helminthes in Worke-mado was 76.7% with S. mansoni being the dominant parasite comprising 64.4% followed by A. lumbricoides (8%). Though not statistically significant, females were more affected than males (35.6% versus 28.7%). Age groups <14 years were more affected than any other groups and was statistically significant. The total prevalence of periportal fibrosis was 9.2% with equal proportion in males and females. The total serum antioxidant (TSA) was 73.1 μmol/L, 70 μmol/L and 305.1 μmol/L in PPF positive, PPF negative and controls respectively. TSA was inversely related with intensity of infection and development of PPF in S. mansoni endemic area.