Loiasis, caused by the filarial nematode Loa loa, imposes a significant burden of disease in endemic regions in West and Central Africa. Manifestations include microfilaria in the blood (MF) and migration of the adult eye worm (EW), with clinical presentations ranging from asymptomatic infections to life threatening organ involvement. The diagnostic gold standard, microscopic detection of microfilaria in the blood, remains difficult due to widely varying microfilaria counts, frequent amicrofilaraemia in patients with EW, and unreliable serological assays. By applying high-throughput plasma proteomics, we investigated the human host response in 274 patients with different L. loa disease states (INF), including EW (n=148), MF (n=42), or both (EWMF; n=84), compared to 136 loa-negative (LN) controls. Five proteins were elevated in INF compared to LN, including IGHG3, IGHG4, and LCP1. Four followed the trend from LN to EW to MF and EWMF, reflecting a more pronounced host response to higher microfilaria couMoMoreover, IGHG4 correlated positively with eosinophil and microfilarial counts underlining its role in chronic, parasitic infections. 63 plasma proteins exhibited notable differences depending on self-reported symptoms. The proteomic signature allowed for accurate classification of EW (AUROC = 0.73) and microfilaria positive (0.84) individuals. Together, L. loa infection leads to relevant alterations of the host plasma proteome, highlighting the importance of further in-depth research on this highly neglected parasitic disease.