Increasing evidence demonstrates that inflammation is associated with many pathophysiologic processes and mortality in older adults. Increase in total white blood cell (WBC) counts is recognized as an important cellular marker of systemic inflammation. However, relationships of total WBC and individual differential counts with mortality in older adults, particularly in older women, have not been adequately evaluated. To address this important question, we obtained baseline total WBC and differential counts and 5-year all-cause mortality of 624 community-dwelling women age 65-101 in the Women's Health and Aging Study cohort, excluding those with WBC counts above the normal range. Using Kaplan-Meier survival and Cox proportional hazard regression analyses, and adjusting for age, race, body mass index, smoking, and education, we identified that baseline higher total WBC, higher neutrophil, or lower lymphocyte counts were independently associated with increased mortality. No significant associations of eosinophil, monocyte, or basophil counts with mortality were observed. These results suggest that beyond acute bacterial infection, changes in counts of baseline total WBC and its specific subpopulations predict increased mortality in older women. They provide a basis for further investigation into the role of leukocytes in age-related inflammation and its associated adverse outcomes in older adults.