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Crimean-Congo haemorrhagic fever (CCHF) is a severe tick-borne viral zoonosis endemic to parts of Africa, Europe, the Middle East and Central Asia. Human cases are reported annually in South Africa, with a 25% case fatality rate since the first case was recognized in 1981. We investigated CCHF virus (CCHFV) seroprevalence and risk factors associated with infection in cattle and humans, and the presence of CCHFV in Hyalomma spp. ticks in central South Africa in 2017–18. CCHFV IgG seroprevalence was 74.2% (95%CI: 64.2–82.1%) in 700 cattle and 3.9% (95%CI: 2.6–5.8%) in 541 farm and wildlife workers. No veterinary personnel (117) or abattoir workers (382) were seropositive. The prevalence of CCHFV RNA was significantly higher in Hyalomma truncatum (1.6%) than in H. rufipes (0.2%) (P = 0.002). Seroprevalence in cattle increased with age and was greater in animals on which ticks were found. Seroprevalence in cattle also showed significant geographic variation. Seroprevalence in humans increased with age and was greater in workers who handled livestock for injection and collection of samples. Our findings support previous evidence of widespread high CCHFV seroprevalence in cattle and show significant occupational exposure amongst farm and wildlife workers. Our seroprevalence estimate suggests that CCHFV infections are five times more frequent than the 215 confirmed CCHF cases diagnosed in South Africa in the last four decades (1981–2019). With many cases undiagnosed, the potential seriousness of CCHF in people, and the lack of an effective vaccine or treatment, there is a need to improve public health awareness, prevention and disease control. Author summary: Crimean-Congo haemorrhagic fever (CCHF) is an infection caused by a tick-borne virus endemic to a large geographic area, that is asymptomatic in animals but presents a significant health risk to humans with no effective vaccine. Serological surveys were carried out in rural populations and animals shortly after the first reported case in South Africa in 1981, but little is known about the current seroprevalence of CCHFV in humans and animals, and tick infection rates. We conducted a survey in 2017–18 to obtain recent estimates and examined exposure factors in an area of South Africa where cases are known to occur. We observed a high seroprevalence in cattle of 74.2%. Farm and wildlife workers at risk of occupational exposure to CCHFV had a seroprevalence of 3.9%, which was higher than previously reported. No evidence of CCHFV infection was found in abattoir workers or veterinary professionals in that area. CCHFV RNA was detected in both species of Hyalomma ticks but with a higher prevalence (1.6%) in H. truncatum. This study suggests that CCHFV is widespread in South Africa, that exposure to CCHFV is more common than generally believed in animal-related occupations and that increased public health awareness of risk factors associated with CCHFV infection are required to reduce morbidity and mortality from CCHF. [ABSTRACT FROM AUTHOR]