Camelpox virus (CMLV) causes a smallpox-like illness in a unique host, the camel.rnAlthough the disease is enzootic in almost all regions where camel husbandry isrnpracticed, and is responsible for severe economic losses, its epidemiology has notrnextensively investigated. Thus, sero- and participatory- epidemiological investigation ofrnthe disease was carried out in Gabi Rasu zone using cross sectional study design torndetermine its seroprevalence and associated risk factors as well as using seasonalrncalendar to identify its seasonal occurrences. In addition camelpox vaccine, the onlyrnavailable vaccine for the species of animal in Ethiopia, was evaluated under fieldrncondition by seroconversion using the before and after with control experimental studyrndesign. The study was conducted in two selected districts of Gabi Rasu zone, fromrnNovember 2014 to May 2015.rnOut of 384 camel sera samples tested by virus neutralization test, 74 were seropositivernfor camelpox, giving an overall seroprevalence of 19.3% (95% CI= 15.3-23.2%) in thernstudy area. A seroprevalence of 21.6 (95% CI= 16.0-27.2) and 16.7 (95% CI=11.2-22.1)rnwere recorded in Amibara and Awash Fentale districts, respectively. At least onernseropositive camel was detected from 25 herds among 30 examined giving 83.3% (95%rnCI = 70.0-96.6) herd level prevalence. Univariable and multivariable logistic regressionrnanalysis of the assumed risk factors showed that age of the camel was the only risk factorrnassociated with the occurrence of serpositivity to camelpox. The results indicated thatrncamelpox seroprevalence was significantly higher in adult (24.4%, 95% CI= 18.4-30.4)rnthan young age group (13.9%, 95% CI= 8.9-18.8) with a 2 fold greater odds ofrnoccurrence. The small-scale vaccine evaluation trial indicated that, vaccination ofrncamels with the live attenuated camelpox vaccine resulted in a significantly higherrnseroconvesrion rate compared to unvaccinated camels. However, among 58 vaccinatedrncamels with pre-vaccination seronegative results, 32 found seropositive at postvaccinationrnserum analysis using VNT, indicating low (55.2%) seroconversion rate.rnVarious explanations have suggested for the failure of post vaccination seroconversionrnon 44.8% vaccinated camels. Interview of pastoralists has revealed that camelpox is onernxrnof the most common camel diseases in the area. The disease was reported commonly tornoccur during the minor (Sugum) and major (Kerma) rainy seasons by informant groups.rnIn conclusion camelpox seems to be endemic in Gabi Rasu zone with seasonalrnoccurrence during rainy season. Therefore, considering the economical significance ofrnthe disease, vaccination of young camels along side training of pastoralists for improvedrnmanagement strategies could have a significant importance in diminishing the virus fromrncirculation. However, further extensive studies that lead to conclusive results on thernefficacy of the vaccine under evaluation are recommended.rnKey words: Afar, Camelpox, Participatory Epidemiology, Risk Factors, Seroprevalence,rnVNT