Update publication information. Onchocerca volvulus, the causative agent of onchocerciasis, infects over 20 million people and can cause severe dermatitis and ocular conditions including blindness. Current mass drug administration treatments do not kill female O. volvulus worms, and common diagnostic tests cannot reliably assess the viability of adult worms. This lack of sensitivity for active infections presents an urgent need for better diagnostic tests to monitor the efficacy of new treatments and ongoing mass drug administration. Serum samples from individuals infected with O. volvulus (n = 8), and from uninfected individuals (n = 7) were examined by deep scale proteomics, including the use of a timsTOF Pro mass spectrometer. Data were interrogated for O. volvulus proteins present in infected but not uninfected samples. Among all detected proteins, 19 high-priority candidate biomarkers were identified in the serum of 3 or more O. volvulus-infected samples (not present in uninfected) that were supported by two or more unique peptides. Comprehensive functional annotation, RNA-seq based transcriptional profiling and taxonomic conservation/diversification characterized the detected proteins in more detail. 15 peptides from 11 of the top 19 proteins were validated by parallel MS/MS (Orbitrap) with isotope-labeled synthetic peptides. One candidate was detected with eight unique peptides in five different serum samples. Additional MS/MS samples have shown that peptides from 4 of the top 6 candidate biomarkers were also detected in urine samples from onchocerciasis patients. We are now working to develop practical assays for the most promising candidates that may be useful for diagnosis of active infections and for monitoring efficacy of new treatments in clinical trials.