Q fever is a zoonotic disease caused by Coxiella burnetii (C. burnetii), an intracellular, Gram-negative bacterium that infects humans and domestic ruminants. Information on flock management factors associated with Q fever seropositivity in Saudi Arabia is very scarce. Therefore, the objective of this study was to identify the animal and flock management factors associated with Q fever seropositivity. For the assessment of risk factors, a case-control study was carried out. Cases (n = 25) were flocks that had recent abortions within the previous two weeks and were PCR positive for C. burnetii. Control flocks (n = 25) had no history of recent abortion and were PCR negative for C. burnetii. A questionnaire was developed to collect information about the flock management risk factors possibly associated with Q fever exposure in sheep. A total of 2437 sheep serum samples, collected from infected (n = 1610, 10–150 samples/flock) and non-infected (n = 827, 10–65 samples/flock) flocks, were tested for C. burnetii antibodies using a commercial ELISA kit between May 2018 and April 2019. In addition, 521 samples, including 50 aborted materials, 173 vaginal swabs, 134 faecal, and 164 milk samples, were collected for PCR testing. Infected flocks were 100% seropositive (within-flock seroprevalence ranging between 13.8% and 60%) and 100% PCR positive (with animal shedders of C. burnetii through aborted materials and/or vaginal fluids, feces, and milk). However, in non-infected control flocks, 28% were seropositive (within-flock seroprevalence ranging between 6.7% and 20%) and none had C. burnetii shedders. Epidemiological data were analyzed using mixed-effect logistic regression with a random effect for the flock. The results identified three protective factors: flocks with a lambing pen (odds ratio (OR): 0.46; 95% CI: 0.28–0.76), change bedding after removing aborted materials (OR: 0.42; 95% CI: 0.23–0.76), and flocks that isolated aborted ewes (OR: 0.41; 95% CI: 0.25–0.67), as well as two risk factors: flocks infested with ticks (OR: 2.78; 95% CI: 1.65–4.70) and flocks with a history of Q fever (OR: 3.03; 95% CI: 1.42–6.50). These results could be used to improve sheep flock biosecurity measures to prevent the introduction and reduce exposure of sheep and humans to Q fever infection.