Toxoplasma gondii infects approximately one third of the population worldwide. There is strong evidence that a relationship between T. gondii titer and depressive symptoms exists. There is also evidence suggesting a protective effect of RhD positive blood factor on toxoplasma-induced behavioral and personality changes. This protective effect may influence the relationship between T. gondii and prenatal depressive symptoms. The purpose of this secondary data analysis was to examine the possible protective effect of RhD positive blood factor on prenatal depressive symptoms in 56 pregnant women with T. gondii infection. The cross-sectional design was utilized to answer the question “Does positive RhD blood factor provide a protective effect on prenatal depressive symptoms of patients infected with T. gondii when controlling for ethnicity, race, income, marital status, age and stress?” The conceptual model hypothesized that there was a relationship between socio-demographic variables (age, income, marital status, race, and ethnicity), stress, positive T. gondii titers, RhD positive blood factor, and prenatal depressive symptoms. Pearson correlations and multiple regression were utilized to explore the aims of this study demonstrated in the four statistical models. Significant relationship between stress and positive T.gondii seropositivity on prenatal depressive symptoms was identified. There was no significant relationship identified between RhD positive blood factor on the pregnant women infected with T. gondii which could be attributed to the small sample size.