Background: Onchocerciasis (river blindness) is a neglected tropical disease that affects the skin and the eye. It is caused by a nematode parasite, Onchocerca volvulus. The disease pathology is largely attributed to host immune responses to the microfilariae. The efficacy of ivermectin (IVM) is defined by its microfilaricidal effects (clearing >60% of microfilariae within 24 h, ∼100% within 7 days) and its ability to temporarily retard the embryogenesis of the adult female parasite at least within 90 days. We sought to profile and compare immune parameters of untreated microfilaremic and IVM-treated amicrofilaremic onchocerciasis patients to identify immune factors differentially associated with microfilaremia. This will help understand the disease mechanism. Methods & Materials: Four bloodless skin biopsies were taken from the two iliac crests and two calves using the corneoscleral punch. The microfilariae emerging from the skin biopsies following overnight incubation in physiological saline in 96-well plate was quantified under the inverted light microscope. We measured white blood cell differentials for 124 adults; 53 microfilaremic (MF) and 71 ivermectin treated (1–5 rounds) seropositive amicrofilaremic (AMF) individuals 3 months following last treatment at the Nkwanta North District of Ghana. Subgroups (16 ≤ n ≤ 20) of both MF and first-time IVM-treated AMF were assayed for plasma cytokines, total serum IgE and urine histamine. Comparisons were made by Mann-Whitney U tests. Results: The geometric mean microfilariae density/milligram skin snip was 22.5 (range 5.8–56.3). Basophil count was lower (p < 0.0001) while eosinophil counts were higher (p = 0.02) for MF compared to AMF. Out of 14 cytokines (IL-1β, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12, IL-13, IFN-γ, TNF-α, GM-CSF and TGFβ); three, Interleukin (IL)-13 (p = 0.002), IL-8 (p = 0.03) and Interferon-gamma (p = 0.003) were higher among MF compared to first time IVM-treated AMF. Histamine and IgE were not different between the two groups. Conclusion: IL-13, IL-8 and interferon-gamma, basophils and eosinophils differentiated between untreated and treated patients and hence these immune parameters might be contributing to the disease pathophysiology among microfilaremic onchocerciasis patients in the Nkwanta North District of Ghana.