Mangrove seedlings are subject to natural tidal inundation, while occasional flooding may lead to complete submergence. Complete submergence reduces light availability and limits gas exchange, affecting several plant metabolic processes. The present study focuses on Rhizophora mucronata, a common mangrove species found along the coasts of Thailand and the Malay Peninsula. To reveal response mechanisms of R. mucronata seedlings to submergence, a physiological investigation coupled with proteomic analyses of leaf and root tissues was carried out in plants subjected to 20 days of control (drained) or submerged conditions. Submerged seedlings showed decreased photosynthetic activity, lower stomatal conductance, higher total antioxidant capacity in leaves and higher lipid peroxidation in roots than control plants. At the same time, tissue nutrient ion content displayed organ-specific responses. Proteome analysis revealed a significant change in 240 proteins in the leaves and 212 proteins in the roots. In leaves, most differentially accumulated proteins (DAPs) are associated with nucleic acids, stress response, protein transport, signal transduction, development and photosynthesis. In roots, most DAPs are associated with protein metabolic process, response to abiotic stimulus, nucleic acid metabolism and transport. Our study provides a comprehensive understanding of submergence responses in R. mucronata seedlings. The results suggest that submergence induced multifaceted stresses related to light limitation, oxidative stress and osmotic stress, but the responses are organ specific. The results revealed many candidate proteins which may be essential for survival of R. mucronata under prolonged submergence.