Objective: Dental caries is associated with immunologic response, yet its association with hematologic parameters and inflammatory markers is unclear. This study aimed to examine the relationship between some surrogate markers of inflammation and dental caries in the context of perinatal exposure to human immunodeficiency virus (HIV). Methods: This cross-sectional study involved 2 groups of children aged 4 to 11 y who were (1) HIV exposed but uninfected (HEU) and (2) HIV unexposed/uninfected (HUU) and recruited from HIV pediatric and child outpatient clinics, respectively, at a tertiary health facility in Nigeria. Medical records were reviewed, and trained dentists conducted oral and dental examinations. Five milliliters of EDTA blood was obtained and used for CD4 and CD8 and complete blood analysis, from which other inflammatory markers such as the neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), systemic inflammatory index (SII), CD4/CD8 ratio were calculated using referenced formulas. Results: In total, 245 (125 HEU and 120 HUU) children with a mean (standard deviation) age of 7 (2) y were included in this study. No differences in caries experience were observed in both groups of children (38 children [16%] were caries affected; 19 [16%] and 19 [15%] from the HEU and HUU groups, respectively). Examining the relationship between studied inflammatory markers and caries showed that leucocyte counts were slightly lower in caries-affected children compared with their caries-free counterparts ( P = 0.05). Lower levels of neutrophils ( P = 0.04) and higher levels of lymphocytes ( P = 0.02) were associated with caries prevalence. Although not significant, NLR, PLR, and SII were lower in caries-affected children. Conclusion: Caries is associated with leucocytes and some of its subsets in both groups of children and independent of perinatal HIV exposure, highlighting the potential of evaluating inflammatory markers in caries prevention, treatment, and research. Knowledge Transfer Statement: This study provides evidence that a relationship exists between dental caries, HIV exposure, and inflammation using affordable methods and advocates the inclusion of these markers in caries care in resource-limited settings.