<p>Estuarine fishes experience marked environmental variability and rely on tightly regulated osmoregulatory mechanisms to maintain internal homeostasis. Settleable atmospheric particulate matter (SePM), a complex mixture of metals and metalloids, is an emerging stressor in aquatic systems and may interfere with regulatory processes. This study investigated the effects of SePM exposure on osmoregulatory homeostasis in the estuarine fish <i>Centropomus parallelus</i>. Fish were exposed for 96&#xa0;h to either 0&#xa0;g.L⁻¹ (control) or 1&#xa0;g.L⁻¹ SePM, and key physiological endpoints associated with ion and water balance were assessed, including plasma osmolality and Na⁺, Cl⁻, and K⁺ concentrations; Na⁺/K⁺-ATPase (NKA), V-type H⁺-ATPase (VAT), and total ATPase activities in the gills and kidneys; and ionocyte abundance and transporter protein levels in gill ionocytes and renal tubules. Aluminum, iron, vanadium, and chromium levels were accumulated in the gills and kidneys. SePM exposure disrupted osmoregulatory homeostasis, as evidenced by reduced plasma osmolality and decreased Cl^– and K⁺ concentrations. NKA activity was upregulated in the gills, accompanied by an increase in the density of NKA-positive ionocytes. Conversely, total ATPase and VAT activities were downregulated in the kidneys, whereas the abundance of NKA, the symporter Na⁺,K⁺,2Cl⁻ (NKCC), and the cystic fibrosis transmembrane conductance regulator (CFTR), a chloride (Cl⁻) channel, remained unchanged in renal tubules. These findings suggest that SePM exposure is associated with tissue-specific modulation of osmoregulatory parameters, including increased branchial Na⁺/K⁺-ATPase activity and NKA-positive ionocyte density, and reduced renal ATPase activities, accompanied by alterations in plasma osmolality and ion concentrations. The physiological disturbances associated with SePM exposure may impair organismal performance and reduce ecological fitness in estuarine fishes inhabiting metal-impacted coastal environments.</p>