BACKGROUND: Almost 1 million pregnant women were estimated to be infected with syphilis in 2016, resulting in over 350,000 adverse birth outcomes including 200,000 stillbirths and new-born deaths (7-9). More than half of infected pregnant women transmit the infection to their babies, resulting in adverse pregnancy outcomes, including foetal death, stillbirth, preterm birth, low birth weight, neonatal death, and congenital infection in infants. OBJECTIVE: The objective of the study was to assess the syphilis status and associated factors among pregnant women attending antenatal care in Kule refugee camp health facilities, Gambella regional state, Southwest Ethiopia, in 2021. METHODS: Facility based cross-sectional study design was conducted among 374 pregnant women in a Kule refugee camp health facility from March 1, to July 15, 2021. A systematic random sampling technique was used to select the study participants. After the interview, 2mL of venous blood sample was drawn from each of the study participants. Then, RPR test was done. When RPR tests were positive, the study subjects were considered as syphilis positive. RESULTS: The overall syphilis positivity rate was 11.8%. Education status (unable to read and write) [AOR 6.6; 95% CI (1.5, 29.3)], presence of other STDs [AOR 3.6; 95% CI (1.4, 8.8)], having polygamy husband [AOR 3.3; 95% CI (1.6, 6.9)] and being HIV positive [AOR=5.5; 95% CI (1.1, 27.5), P=0.04] were among factors associated with syphilis infection. CONCLUSIONS AND RECOMMENDATION: This study showed that there is very high syphilis prevalence and it is still a very important public health problem the study area. Therefore, syphilis screening and treatment of pregnant women towards the first ANC points and health education towards the mode of transmission and prevention of syphilis have to be strengthened.