BackgroundHyperkalemia is a frequently observed electrolyte imbalance in dehydrated neonatal diarrheic calves that can result in skeletal muscle weakness and life‐threatening cardiac conduction abnormalities and arrhythmias.HypothesisIntravenous administration of a small‐volume hypertonic NaHCO3 solution is clinically more effective in decreasing the plasma potassium concentration (cK) in hyperkalemic diarrheic calves than hypertonic NaCl or glucose solutions.AnimalsTwenty‐two neonatal diarrheic calves with cK >5.8 mmol/L.MethodsProspective randomized clinical trial. Calves randomly received either 8.4% NaHCO3 (6.4 mL/kg BW; n = 7), 7.5% NaCl (5 mL/kg BW; n = 8), or 46.2% glucose (5 mL/kg BW; n = 7) IV over 5 minutes and were subsequently allowed to suckle 2 L of an electrolyte solution. Infusions with NaHCO3 and NaCl provided an identical sodium load of 6.4 mmol/kg BW.ResultsHypertonic NaHCO3 infusions produced an immediate and sustained decrease in plasma cK. Hypertonic glucose infusions resulted in marked hyperglycemia and hyperinsulinemia, but cK remained unchanged for 20 minutes. Between 30 and 120 minutes after initiation of treatment, the most marked decrements in cK from baseline occurred in group NaHCO3, which were significantly (P < .05) larger during this period of time than in calves in group NaCl, but not group glucose. After 120 minutes, the mean decrease in cK from baseline was −26 ± 10%, −9 ± 8%, and −22 ± 6% in groups NaHCO3, NaCl, and glucose, respectively.Conclusions/Clinical ImportanceSmall‐volume hypertonic NaHCO3 infusions appear to have clinical advantages for the rapid resuscitation of hyperkalemic diarrheic calves, compared to hypertonic NaCl or glucose solutions.