Migratory fishes encounter a variety of environmental conditions, including changes in salinity, temperature and dissolved gases, and it is important to understand how these fishes are able to acclimate to multiple environmental stressors. The gill is the primary site of both acid-base balance and ion regulation in fishes. Many ion transport mechanisms involved with acid-base compensation are also required for the regulation of plasma Na(+) and Cl(+), the predominant extracellular ions, potentially resulting in a strong interaction between ionoregulation and acid-base regulation. The present study examined the physiological interaction of elevated dissolved CO2 (an acid-base disturbance) on osmoregulation during seawater acclimation (an ionoregulatory disturbance) in juvenile white sturgeon (Acipenser transmontanus). Blood pH (pHe), plasma [HCO3 (-)], [Na(+)], [Cl(-)] and osmolality, white muscle water content, and gill Na(+)/K(+)-ATPase (NKA) and Na(+)/K(+)/2Cl(-) co-transporter (NKCC) abundance were examined over a 10 day seawater (SW) acclimation period under normocarbia (NCSW) or during prior and continued exposure to hypercarbia (HCSW), and compared with a normocarbic freshwater (NCFW) control. Hypercarbia induced a severe extracellular acidosis (from pH 7.65 to pH 7.2) in HCSW sturgeon, and these fish had a 2-fold greater rise in plasma osmolarity over NCSW by day 2 of SW exposure. Interestingly, pHe recovery in HCSW was associated more prominently with an elevation in plasma Na(+) prior to osmotic recovery and more prominently with a reduction in plasma Cl(-) following osmotic recovery, indicating a biphasic response as the requirements of osmoregulation transitioned from ion-uptake to ion-excretion throughout SW acclimation. These results imply a prioritization of osmoregulatory recovery over acid-base recovery in this period of combined exposure to acid-base and ionoregulatory disturbances.