Background Reliable biomarkers for monitoring disease progression and management in dogs with acute pancreatitis have not been described. Objective To determine if serum concentrations of canine pancreatic lipase immunoreactivity (cPLI) and C‐reactive protein (CRP) can be used as biomarkers for disease progression in hospitalized dogs with acute pancreatitis. Animals Thirteen hospitalized dogs with acute pancreatitis diagnosed based on clinical signs, serum cPLI concentrations, and imaging findings were enrolled. Methods Serum cPLI and CRP concentrations were determined before and then daily during hospital management and 1 week after hospital discharge. Modified canine activity index (MCAI) and canine acute pancreatitis clinical severity index (CAPCSI) scores were calculated daily for each patient while hospitalized. Results The MCAI scores (P = .03) but not CAPCSI scores (P = .31) were significantly different between dogs that survived to discharge (n = 11) and those that did not (n = 2). Serum cPLI concentration was positively correlated with MCAI (rho = 0.42; P = .01). Serum CRP concentration also was positively correlated with the MCAI (rho = 0.42, P = .01). Conclusions Serum cPLI and possibly CRP could be used as objective biomarkers for clinical changes in hospitalized dogs with acute pancreatitis. Additional studies involving larger numbers of dogs would be warranted to evaluate the broader impact of these findings.