Recent research indicates that microplastic (<5 mm) ingestion may impact the immune function of marine and aquatic organisms at the tissue and cellular levels; however, their susceptibility to disease following exposure has not been directly investigated. The objective of the present study was to directly evaluate the impact of microplastic ingestion on the susceptibility of the grass shrimp Palaemonetes pugio to bacterial infection with Vibrio campbellii. Grass shrimp were exposed to one of several particle treatments (natural sediment, polyethylene spheres, polypropylene fragments, tire fragments, and polyester fibers) or particle‐free water for 96 h at a nominal concentration of 50 000 particles/L prior to a bacterial challenge with V. campbellii. No significant mortality was observed among any of the particle types during the 96‐h particle exposure. The survival of grass shrimp following V. campbellii challenge did not vary significantly among shrimp exposed to particle‐free water, sediment, polyethylene spheres, polypropylene fragments, tire fragments, and polyester fibers. Grass shrimp cleared the majority of ingested particles and all the ventilated particles within 48 h. The present study shows that microplastic ingestion did not alter the susceptibility of grass shrimp to bacterial infection, and also provides depuration rates for a variety of microplastic shapes and polymer types that were previously lacking. This information increases our understanding of the size‐ and shape‐dependent effects of microplastic ingestion. Environ Toxicol Chem 2019;38:2233–2242. © 2019 SETAC.