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Abstract In marine habitats, Atlantic salmon (Salmo salar) imbibe seawater (SW) to replace body water that is passively lost to the ambient environment. By desalinating consumed SW, the esophagus enables solute‐linked water absorption across the intestinal epithelium. The processes underlying esophageal desalination in salmon and their hormonal regulation during smoltification and following SW exposure are unresolved. To address this, we considered whether two Na⁺/H⁺exchangers (Nhe2 and −3) expressed in the esophagus contribute to the uptake of Na⁺from lumenal SW. There were no seasonal changes in esophagealnhe2or−3expression during smoltification; however,nhe3increased following 48 h of SW exposure in May. Esophagealnhe2, −3, andgrowth hormone receptor b1were elevated in smolts acclimated to SW for 2.5 weeks. Treatment with cortisol stimulated branchial Na⁺/K⁺‐ATPase (Nka) activity, andNa⁺/K⁺/2Cl⁻cotransporter 1(nkcc1),cystic fibrosis transmembrane regulator 1 (cftr1), andnka‐α1bexpression. Esophagealnhe2, but notnhe3expression, was stimulated by cortisol. In anterior intestine, cortisol stimulatednkcc2, cftr2, andnka‐α1b. Our findings indicate that salinity stimulates esophagealnhe2and−3, and that cortisol coordinates the expression of esophageal, intestinal, and branchial solute transporters to support the SW adaptability of Atlantic salmon.