Sterile triploid Atlantic salmon (Salmo salar) show inconsistent seawater grow-out, but the reason why remains unclear. The purpose of this study was to determine the salinity optima of triploid post-smolts. Diploids and triploids were assessed for smoltification status during an underyearling smolt regime before being transferred to one of four different salinities, 0, 11, 23 and 35 ppt at 12 °C and under 24 h continuous light for 83 days. During this period, fish growth, plasma biochemistry, and production traits (vertebral deformities, ocular cataracts, sexual maturation) were monitored. Molecular biomarkers in the gill (nkaα1a, nkaα1b, nkcc1a) suggested triploids reached peak smolt earlier than diploids and began the desmoltification process before the start of the salinity treatments, however this was not reflected in gill Na⁺/K⁺-ATPase enzyme activity. At the initiation of the salinity treatments triploids were significantly larger than diploids (mean weight g ± SE: 71 ± 0.7 and 87.2 ± 0.8 for diploids and triploids, respectively) and there was a ploidy effect on post-smolt growth, with body weight showing a clearer positive trend with salinity in diploids (0 < 11 = 23 = 35 ppt) than in triploids (0 < 11 < 35 = 23 ppt) (final mean weight g ± SE: 255.2 ± 7.4, 303.9 ± 9, 313.9 ± 9 and 342.4 ± 12 for diploids and 322.9 ± 9.7, 361.7 ± 10.7, 425.9 ± 12.1, 415.2 ± 12.2 for triploids at 0, 11, 23, and 35 ppt, respectively). Plasma Na⁺ and Cl⁻ increased, but plasma pH decreased, with increasing salinity in both ploidy. However, ploidy only had transient effects on plasma biochemistry depending on the salinity treatment. There was no ploidy effect on vertebral deformities (21% of both ploidy had one or more deformed vertebra). In contrast, triploids had a significantly higher prevalence of ocular cataracts (84 vs 98% in diploids and triploids, respectively) with a higher mean cataract score (mean ± SE: 1.93 ± 0.1 and 2.78 ± 0.1 for diploids and triploids, respectively), but a significantly lower prevalence of pubertal male post-smolts (15 vs 2% in diploids and triploids, respectively). Salinity treatment had no effect on vertebral deformities, cataracts, or post-smolt sexual maturation. In summary, there was a ploidy mismatch for smoltification biomarkers in the gill and salinity had a strong effect on post-smolt growth, but the effects were ploidy dependent.