Chronic lymphedema caused by infection ofWuchereria bancroftiis a disfiguring disease that leads to physical disability, stigmatization, and reduced quality of life. The edematous changes occur mainly on the lower extremities and can progress over time due to secondary bacterial infections. In this study, we characterized participants with filarial lymphedema from Ghana and Tanzania as having low (stage 1–2), intermediate (stage 3–4), or advanced (stage 5–7) lymphedema to determine CD4+T cell activation patterns and markers associated with immune cell exhaustion. A flow cytometry-based analysis of peripheral whole blood revealed different T cell phenotypes within participants with different stages of filarial lymphedema. In detail, increased frequencies of CD4+HLA-DR+CD38+T cells were associated with higher stages of filarial lymphedema in patients from Ghana and Tanzania. In addition, significantly increased frequencies of CCR5+CD4+T cells were seen in Ghanaian participants with advanced LE stages, which was not observed in the Tanzanian cohort. The frequencies of CD8+PD-1+T cells were augmented in individuals with higher stage lymphedema in both countries. These findings show distinct activation and exhaustion patterns in lymphedema patients but reveal that immunological findings differ between West and East African countries.