Antibiotic restrictions in swine have increased interest in alternative feed additives to support intestinal health and immunity during the post-weaning period. Based on previous findings, this study evaluated the effects of heat-killed Mycolicibacterium manresensis (hkMm) on cellular, humoral, and innate immunity in weaned piglets. Four-week-old piglets were randomly allocated into three groups (n=5) receiving a control diet or diets supplemented with 10 or 50 ppm hkMm. At day 70, duodenal and jejunal samples were collected and analyzed by immunohistochemistry using markers for T cells (CD3, TCRδ, and FoxP3), IFN-γ⁺ cells, B cells (CD20), IgA-producing cells, and macrophages (CD163). Supplemented animals showed increased numbers of CD3⁺, particularly TCRδ⁺ and FoxP3⁺ subsets, resulting in higher TCRδ/CD3 and FoxP3/CD3 ratios. hkMm also enhanced humoral and mucosal immune responses, as indicated by increased numbers of CD20⁺ B cells and IgA+ cells, especially at 10 ppm (p = 0.04). CD163⁺ macrophages showed slight increases, suggesting enhanced regulatory and homeostatic mechanisms, while a moderate increase in jejunal IFN-γ⁺ cells was observed at 10 ppm. Correlation analysis revealed positive associations between CD3 and TCRδ (r = 0.53; p = 0.05), and betweeen TCRδ and CD163 in the jejunum (r = 0.70; p = 0.01), whereas CD163 was negatively associated with IFN-γ in the duodenum (r = −0.53; p = 0.04). Overall, the 10 ppm dose elicited the most consistent responses, promoting coordinated changes in cellular, humoral, and innate immunity. These findings suggest that hkMm may enhance mucosal immune competence while supporting intestinal homeostasis during the post-weaning period.