HIV and malaria are predominant co-infections prevalence in Nigeria, and are found in pregnant women. This is a case – control study aimed at evaluating the Levels of Interleukins -6 (IL-6), Interleukins -10 (IL-10), Tissue Necrotic Factor Alpha (TNF-α), Noepterin (NPT), C- Reactive protein (CRP), Total protein and Albumin in HIV – malaria co –infected pregnant women in Nigeria. A total of 100 participants with aged range of 29.18±04) years were randomly recruited for the study. The participants were grouped as follows :( a) 100 HIV positive pregnant women without malaria infection (b) 100 HIV positive pregnant women with malaria infection (c) 100 HIV negative pregnant women with Malaria Infection and (d) HIV negative Pregnant women without malaria infection. Using a one-step pregnancy test strip made by ACON Laboratories Inc. in the USA, research participants had their urine tested for Human Chorionic Gonadotropin (HCG) to determine whether they are pregnant. Eight (8) ml of blood was collected from each participant for the measurement of serum levels of Interleukins -6, Interleukins -10, Tissue Necrotic Factor Alpha (TNF-α), Noepterin, C- Reactive protein, Total protein, Albumin and CD4 counts using standard laboratory methods.. They all underwent HIV detection and screening by rapid Immunochromatographic Immunoassay techniques (Abbott Japan Co.Ltd. Tokyo, Japan and CHEMBIO Diagnostic system, Inc, New York, USA.). Plasmodium falciparum detection and screening- using Giemsa stained thick and thin blood films and rapid chromatographic immunoassay for qualitative detection in blood. Analysis of variance (ANOVA) and student t test were used for data analyses. The result showed that the mean CD4 count was significantly reduced in HIV positive pregnant women without malaria infection than in those with malaria parasitemia at P<0.05. The serum IL-6 was significantly higher in HIV negative pregnant women without malaria infection than in control group at P<0.05.Also, the serum IL-6 was significantly higher in HIV positive pregnant women with malaria infection than in HIV positive pregnant women with Malaria Infection at P<0.05. The serum IL-10 were significantly higher in HIV negative pregnant women without malaria infection and in HIV positive pregnant women with malaria infection when compared with HIV negative pregnant women with malaria parasitemia at P<0.05 respectively. The serum CRP was significantly lower in HIV positive pregnant women without malaria infection than in those with malaria parasitemia but the value was lower in HIV positive pregnant women with malaria infection than in controls P<0.05 respectively. The mean serum total protein and albumin were significantly lower in HIV positive pregnant women without malaria infection than in HIV positive pregnant women with malaria infection but their values were significantly higher in HIV positive pregnant women with malaria infection P<0.05 in each case. The mean serum TNF-α was significantly lower in HIV positive pregnant women without malaria infection than in those with malaria infection but TNF-α and neopterin levels were significantly higher in HIV positive pregnant women without malaria infection and in those with malaria infection when compared with the controls at P<0.05 respectively.