Human immunodeficiency virus (HIV) infection is a global pandemic with frightening mortality and morbidity, no effective vaccine and curative treatment though it is preventable. Globally heterosexual and vertical transmissions remain the leading means of its spread. The sub Saharan African female adults are the most affected and most of the world HIV positive children were from vertical transmission. Therefore an in-depth knowledge of the women HIV risk factors is crucial to its effective prevention and control. The general objective of this study was to investigate the association between sociodemographic and bio-clinical variables and HIV infection in pregnancy. The specific objectives were to determine the prevalence of HIV infection among pregnant women and to compare the sociodemographic profiles and the bio-clinical variables of HIV seropositive mothers and matched seronegative counterparts. This was a retrospective case control analysis of 116 HIV positive mothers as study group and 232 HIV negative mothers as control group. The data used was obtained from the records of women that delivered between 2009 and 2013 in a mission hospital, in Benin City, Edo state, South-south, Nigeria. Statistical analyses of the data were done, P-value of 0.05 was considered as significant. Our results indicated that the prevalence of HIV seropositivity in pregnancy in this setting was 2.94%. HIV Seroprevalence was statistically significant different among women aged 25-29 years (p=0.048) and 30-34 years (p=0.01), with low (primary) educational attainment (p=0.048) and in government employment (OR.0.25, P=0.006). The seropositive mothers had significantly lower haematocrit (P=0.0015), higher incidence of anemia at booking (P=0.0023) and reduced weight gain at term (P=0.013). Their newborns significantly weighed less at birth (P=0.0032), suffered intrauterine growth restriction (P=0.0002) and low birth weight (P=0.0017). HIV infection in pregnancy is still a significant burden. It appears to have social predictors and materno-fetal health implications. We therefore recommend sustained efforts at personal level especially behavioral and lifestyle adjustment, collective and at government level female gender empowerment to control the scourge.