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Bycatch interactions with deep-sea elasmobranchs are increasingly common and can lead to dramatic declines in abundance over short time scales. Sharks hooked in the deep sea could face a higher likelihood of severe physiological disturbance, at-vessel mortality, and post-release mortality (PRM) than their shallower counterparts. Unfortunately, robust PRM rates have not yet been estimated for longline-caught deep-sea sharks, and as such are not currently incorporated into total fishery mortality estimates or bycatch assessments, limiting the effectiveness of current conservation or management initiatives. We empirically estimated PRM for 2 focal taxa of deep-sea shark, the Cuban dogfish Squalus cubensis and the gulper shark Centrophorus sp., using post-release enclosures deployed at-depth. We calculated 24 h PRM rates of 49.7 ± 8.5% (mean ± SE) for S. cubensis and 83 ± 16% for Centrophorus sp. and identified blood lactate, total length, glucose, and vitality scores as predictors of PRM in S. cubensis. We also observed all 24 h PRM within 11 h post-capture and demonstrated the effects of recovery depth and at-vessel blood chemistry metrics on post-release behavior. Our results suggest that PRM rates of deep-sea sharks are high and highlight the need for filling in this gap in fishery mortality estimates for other common discards in the future.