We analyzed blood serum samples from two unique female occupational cohorts - 60 nurses and 40 office workers in San Francisco, CA - using liquid chromatography and high-resolution mass spectrometry (quadrupole time-of-flight). Applying a nontargeted analysis (NTA) approach, we sought to isolate occupationally related chemical exposures that were unique to nurses by flagging features that were different from office workers in abundance (mean
95th percentile) or detection frequency. Of 9828 negative electrospray ionization (ESI-) and 6898 positive electrospray ionization (ESI+) detected chemical features, 1094 and 938, respectively, were higher in nurses, possibly due to workplace exposures. We deciphered the molecular structures of these chemical features by applying data-dependent acquisition (DDA) and targeted MS/MS approaches to pooled samples from each occupational group, and we annotated them using spectral MS/MS databases in MS-DIAL. Nurses had higher concentrations of 14 chemicals that we identified at Schymanski Level 1 (N = 6) or 2 (N = 8), as well as 20 tentatively identified chemicals without spectra. Several chemicals may be occupationally relevant for nurses, including a PFAS (6:2 fluorotelomer sulfonic acid), tridecanedioic acid, salicylic acid, and the medications acetaminophen and theophylline. To our knowledge, this study is the first to apply NTA to elucidate novel chemical exposures in nurses.