A dangerous zoonotic bacterial infection that has a significant financial impact on the sheep industry is Chlamydophila spp. This investigation's aims were to determine the prevalence of Chlamydophila spp infection, study particular risk indicators, and assess the antioxidant status and biochemical changes of infected sheep. One hundred sheep were used in this study. Whole blood and serum samples were collected for laboratory analysis. ELISA and PCR had been employed for Chlamydophila spp diagnosis. The observed clinical findings of Chlamydophila spp infection in sheep were abortion, infertility, respiratory signs, conjunctivitis, diarrhea, and nervous manifestations. The seroprevalence of Chlamydophila spp infection was 2.20% (2/91) using ELISA. Of the studied sheep, 89 (89%) and 76 (76%) of 100 whole blood samples showed molecularly positive results for Chlamydophila spp, 16S rRNA and OMP2 genes, respectively. The infection rate of Chlamydophila spp had no significant variation by age and sex of infected sheep, but prevalence of Chlamydophila spp infection was significantly higher in autumn and winter, on farms, and in clinically diseased sheep. The concentration of TAC in the serum of Chlamydophila spp-infected sheep was significantly higher compared to healthy animals. The mean concentration of total protein, albumin, and GGT in Chlamydophila spp-infected sheep did not differ significantly from clinically healthy ones. It is essential to highlight the importance of efficient preventative and control measures throughout Egypt to reduce the prevalence of Chlamydophila spp infection in sheep.