Bovine coronavirus (BCoV) is a common viral enteric pathogen responsible for diarrhea in newborn calves. Despite its economic significance, there is limited research on this virus in Egypt. This study aimed to detect the prevalence of BCoV, the associated risk factors, and the biochemical changes during infection. A cross-sectional study included 196 pre-weaned diarrheic calves chosen randomly from 16 farms. Fecal samples were obtained from these diarrheic calves, and a questionnaire was administered to investigate the positivity of BCoV and the potential risk factors. Moreover, blood samples were collected to evaluate the biochemical changes in the infected calves. Logistic regression models were used to assess the strength of the risk factors associated with bovine coronavirus. The prevalence of BCoV among pre-weaned diarrheic calves was 11.22%. The final multivariate analysis revealed that the infection of BCoV was 3.8, 5.96, and 3.2 times higher in males, age ≥ 15 days, and winter season than in female calves, age <
15 days, and other seasons, respectively. The acute phase proteins and the inflammatory biomarkers were changed in infected calves compared to healthy ones. The results indicated that calf age, gender, and exposure to cold temperatures were potential risk factors for BCoV infection. Conversely, no evidence was found to support the hypothesis that BCoV prevalence is linked to locality or ground type. Moreover, the observed biochemical changes in calves with BCoV could assist in the early diagnosis of the infection and provide valuable insights for evaluating prognosis.