In the present study, the peripheral blood leukocyte phenotypes, lymphocyte subset populations, and oxidative stress parameters were studied in cognitively characterized adult and aged dogs, in order to assess possible relationships between age, cognitive decline, and the immune status. Adult (N = 16, 2-7 years old) and aged (N = 29, older than 8 years) dogs underwent two testing procedures, for the assessment of spatial reversal learning and selective social attention abilities, which were shown to be sensitive to aging in pet dogs. Based on age and performance in cognitive testing, dogs were classified as adult not cognitively impaired (ADNI, N = 12), aged not cognitively impaired (AGNI, N = 19) and aged cognitively impaired (AGCI, N = 10). Immunological and oxidative stress parameters were compared across groups with the Kruskal-Wallis test. AGCI dogs displayed lower absolute CD4 cell count (p < 0.05) than ADNI and higher monocyte absolute count and percentage (p < 0.05) than AGNI whereas these parameters were not different between AGNI and ADNI. AGNI dogs had higher CD8 cell percentage than ADNI (p < 0.05). Both AGNI and AGCI dogs showed lower CD4/CD8 and CD21 count and percentage and higher neutrophil/lymphocyte and CD3/CD21 ratios (p < 0.05). None of the oxidative parameters showed any statistically significant difference among groups. These observations suggest that alterations in peripheral leukocyte populations may reflect age-related changes occurring within the central nervous system and disclose interesting perspectives for the dog as a model for studying the functional relationship between the nervous and immune systems during aging.