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Abstract Background The Crimean-Congo Hemorrhagic fever (CCHF) is endemic in Iran and has a high fatality rate. The aim of this study was to investigate the association between CCHF incidence and meteorological variables in Zahedan district, which has a high incidence of this disease. Methods Data about meteorological variables and CCHF incidence was inquired from 2010 to 2017 for Zahedan district. The analysis was performed using univariate and multivariate Seasonal Autoregressive Integrated Moving Average (SARIMA) models and Generalized Additive Models (GAM) using R software. AIC, BIC and residual tests were used to test the goodness of fit of SARIMA models, and R2 was used to select the best model in GAM/GAMM. Results During the years under study, 190 confirmed cases of CCHF were identified in Zahedan district. The fatality rate of the disease was 8.42%. The disease trend followed a seasonal pattern. The results of multivariate SARIMA showed the (0,1,1) (0,1,1)12 model with maximum monthly temperature lagged 5 months, forecasted the disease better than other models. In the GAM, monthly average temperature lagged 5 months, and the monthly minimum of relative humidity and total monthly rainfall without lag, had a nonlinear relation with the incidence of CCHF. Conclusions Meteorological variables can affect CCHF occurrence.