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Mussel mariculture uses the natural attachment strategy of marine mussels by allowing them to aggregate on submerged rope lines that are then pulled to the surface and harvested. Mussels attach to ropes using a network of byssal threads, proteinaceous fibers that adhere to surfaces underwater using a powerful biological glue (adhesive plaque). Plaques use the surrounding seawater as a molecular trigger during adhesive curing, a process that requires a pH greater than 7.0 and an abundance of dissolved oxygen to progress. To ascertain whether mussels experience seawater conditions that are potentially harmful to mussel attachment, this study measured the conditions within mussel aggregations at a mussel farm in Washington state and, then, applied those conditions to plaques to determine whether such conditions are sufficient to weaken attachment. Seawater monitoring demonstrated that mussels infrequently experience acidic (pH <5.0) and hypoxic excursions (O2 <2 mg L–1) in the summer, especially near the seafloor. When reproduced in laboratory assays, the most extreme pH excursions observed delayed plaque strengthening when applied early in the plaque-curing process, whereas extreme excursions in hypoxia decreased adhesion strength after the adhesive had fully matured. In either case, adhesion strength was rescued after reimmersion in open-ocean seawater conditions, highlighting the resilience of the mussel holdfast to stresses other than mechanical strain. The window of susceptibility to changes in environmental conditions during and after curing could contribute to fall-off events at mussel farms, especially in the late summer months. [ABSTRACT FROM AUTHOR]