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Background: Crimean-Congo hemorrhagic fever (CCHF) is a prevalent tick-borne disease in different regions of Iran. This molecular and serologic study was performed to investigate the Crimean-Congo hemorrhagic fever virus (CCHFV) in collected ticks and in blood samples of some domestic animals in North Khorasan, Northeast of Iran. Methods: In this cross sectional study, 136 blood samples from domestic animals (sheep, goats, and cows) collected in the Northeast region in Iran were examined using IgG ELISA assay. Ticks (n = 1478) were collected from sheep, goats, and cows. Out of all collected ticks, 62 specimens were investigated for CCHF virus genome using RT-PCR technique. The data were descriptively presented by median and 95% confidence interval (CI). Results: CCHFV infection rate was 8.1% in studied ticks. Two species of ticks, Hy. anatolicum (n=3; 15%, 95% CI 9.41–20.59) and Rh. sanguineus (n=2; 6.9%, 95%CI 4.33–8.58), were infected with CCHFV genome and were probable vectors of CCHF virus in the area. Infection rate was 15.4% for CCHFV in tested domestic animals. Serologic tests detected CCHFV specific IgG antibodies in 16.2% (95% CI 13.49–18.83) (99/16) and 19.2% (95% CI 13.26–25.20) (26/5) of sheep and goats, respectively. Conclusion: The present study showed that domestic animals and ticks were infected with Crimean-Congo hemorrhagic fever virus and that the disease was endemic in North Khorasan province, Iran. However, further surveillance and prevention programs are recommended.