Abstract: A cross-sectional study to investigate Peste des Petits Ruminants (PPR) seroprevalence was conducted between November 2014 and May 2015 in selected districts of Siltie and Gurage zones, South Region, Ethiopia. A total of 390 serum samples were collected from sheep and goats. Competitive Enzyme Linked Immunosorbent Assay (c-ELISA) was used to detect the presence of antibodies in the sera of animals as indicator of exposure to the PPR virus. The total apparent prevalence was found to be 29.2% (114/390), indicating the spread of PPR virus throughout the study areas with Silti and Meskan Districts experiencing the prevalence of 24.2 and 33%, respectively. Study animals were categorized into two age groups as young and adult with prevalence of 25.9 and 31.8%, respectively. Out of total 390 samples, 240 serum samples were from male and 150 serum samples from female with prevalence of 29.6% (71/240) and 28.66% (43/150), respectively. In the two animal species the distribution of PPR virus was observed with the prevalence of 24.2% (46/190) in sheep and 34% (68/200) in goats. Statistically significant difference (p<0.05) was observed between the two study areas and species whereas the seroprevalence of PPR was statistically insignificant (p>0.05) in other hypothesized risk factors. This study revealed circulation and subsequent endemic establishment of PPR in sheep and goats in the selected study areas. This disease is detrimental to small ruminant welfare and causes substantial economic losses, thereby affecting the livelihood of poor farmers and pastoralists. The need for implementing feasible control measures is therefore, eminent to minimize the losses associated with the disease.