There is an overlap in the symptoms of the human immunodeficiency virus (HIV) infection and vitamin B12 insufficiency; thus, both should be diagnosed and treated promptly. This investigation aimed to examine the relationship between vitamin B12 levels in the blood of people with a recent HIV diagnosis and other variables such as CD4 and CD8 cell counts, clinical staging, and hematological profiles. Around 55 adults with a confirmed HIV infection who were at least 18 years old were recruited, along with the same number of controls of the same age and gender. Flow cytometry measured CD4 and CD8 cell populations. C-reactive protein (CRP) levels, complete blood count, folic acid, ferritin, and vitamin B12 in serum were also measured. HIV-positive cases had a considerably lower serum Vitamin B12 level than healthy controls (240.62 ± 56.75 pg/ml vs. 317.57 ± 52.56 pg/ml, respectively). Patients with HIV had lower CD4 counts and higher ferritin and CRP values. Subgroup analysis based on vitamin B12levels showed a positive correlation with CD4 counts. There was also a statistically significant correlation between CD8 cell counts and blood B12 levels, but this effect was not linear with the severity of vitamin B12 insufficiency. About 1/3rd  of people who tested positive for HIV also had low levels of vitamin B12. A lack of vitamin B12 can develop in the first place because of the increased consumption of micronutrients caused by rapidly dividing immune cells. In addition to increasing the number of CD8 cells, it leads to methylation problems that impair immune function and decrease NK cell activity. Vitamin B12 is an effective immunological modulator of HIV infection, which can be a game-changer in low-resource settings.