Background Lumpy skin disease (LSD) is one of Ethiopia’s most economically significant transboundary livestock illnesses. The disease has a significant economic impact on pastoral household livestock owners, who rely significantly on their cattle as a source of income. Methods A cross-sectional study was undertaken in selected districts of Afar region from November 2018 to May 2019 primarily intended to estimate the prevalence of lumpy skin disease serologically in local Afar cattle as well as identify potential associated factors. A multistage sampling method was employed to select study districts, peasant association, herd size and study units. A total of 384 sera were processed using serum neutralization test (SNT) method to detect antibodies against lumpy skin disease virus. Relevant data were refined and further analyzed using stata version 14. Results In the study districts, the overall animal level seroprevalence was found to be 7.6% (N = 29/384; 95% confidence interval: 4.90–10.20) and the overall herd level prevalence was found to be 20.8% (n = 15/72; 95% confidence interval: 11.42–30.18). Only district was shown to be statistically significant (P = 0.004) in terms of LSD occurrence among the relevant factors studied. Cattle in Chifra district were 20.18 times more likely to contract LSD infection than cattle in Dubti district, when Asayita district was used as the reference group. Conclusion The present study finding confirmed the presence of the disease in the study districts of afar region and coordinated intervention set to be in place.

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