Human immunodeficiency virus (HIV) continues to be a major global public health issue and omnipresent sexually transmitted infections (STIs) increase the risk of HIV acquisition. Moreover, STIs and HIV in pregnant women can harm the unborn child. In this study, we systematically investigated the prevalence of HIV, relevant STIs and vaginal group B streptococcus colonization among pregnant women presenting at Asella Teaching Hospital in central Ethiopia and their effect on perinatal mortality. A follow-up was performed six weeks after delivery. A total of 580 women were included, of which 26.6% tested positive for at least one pathogen ( Chlamydia trachomatis 9.8%, trichomoniasis 5.3%, hepatitis B 5.3%, gonorrhoea 4.3%, group B streptococcus 2.4%, syphilis 2.2%, HIV 2.1%). None of the HIV infections were previously undiagnosed, indicating effective HIV screening activities in the region. Follow-up data were available for 473 (81.6%) children, of which 37 (7.8%) were stillborn or died within the first six weeks of life. Infection with Trichomonas vaginalis and recruitment at obstetric ward (versus antenatal care) were associated with mortality. High prevalence of STIs in pregnant women and their impact on the unborn child demonstrate the need for screening and treatment programmes in order to prevent perinatal mortality.