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Leptospirosis is a zoonotic disease that can affect multiple organs with renal and hepatic involvement being considered to be the most common. The aim of this study was to evaluate a large number of dogs with leptospirosis for cardiac and/or exocrine pancreatic involvement. A total of 59 dogs were diagnosed with leptospirosis based on clinical signs and either microscopic agglutination test, blood/urine polymerase chain reaction, and/or histopathology. At the time of admission and, in most patients, after an average of two weeks canine pancreatic lipase immunoreactivity (cPLI, as measured by Spec cPL), ultrasensitive cardiac Troponin I (cTnI), and C-Reactive Protein (CRP) were analyzed. Data were analyzed with non-parametric statistics. The level of significance was set at p < 0.05. Upon admission, common clinical signs reported included lethargy (n = 57), vomiting (n = 50), abdominal pain (n = 20), dyspnea (n = 16), pale mucous membranes (n = 13), oliguria (n = 11), hypothermia (n = 11), and fever (n = 10). Anemia (n = 39), thrombocytopenia (n = 41), leukocytosis (n = 38), were frequently reported hematology findings. Increased concentrations of creatinine (n = 48/59), phosphorus (n = 43/57), ALT (n = 31/58), SAP (n = 43/57) and bilirubin (n = 41/58) were also frequently recorded. CRP (median: 48.7 mg/L; range: 0.1-60.1 mg/L, reference interval (RI): 0.1-7.6 mg/L), cTnI (median: 0.137 ng/L; range: 0.005-24.063 ng/L, RI: 0-0.059 ng/L), and cPLI (median: 217 lg/L; range: 29-1001 lg/L, RI: 0-200 lg/L) concentrations were above the upper limit of the reference intervals in 52/59 (88%), 42/59 (71%), and 30/59 (51%) dogs, respectively and serum cPLI concentration was above the suggested cut-off value for a diagnosis of pancreatitis in 15/59 (25%) dogs. CRP and cTnI, but not cPLI were higher upon admission compared to the re-check measurement (p = 0.0001 and 0.0056, respectively). Dogs with increased serum cPLI concentrations also showed a higher proportion of dogs with increased serum cTnI concentrations (p = 0.001). There was no statistically significant correlation of cPLI concentrations with a history of abdominal pain and/or vomiting. Biochemical results were compatible with multiple organ impairment with involvement of kidneys, liver, heart, and exocrine pancreas where at least two organs were affected in 36/59 (61%) dogs. Forty (68%) of 59 dogs recovered, 10 (17%) died, and 9 (15%) were euthanized. cTnI and cPLI were higher in non-survivors, but these differences did not reach statistical significance. However, the number of organs affected and outcome were significantly correlated (p = 0.012). Our data suggest that infection with Leptospira is characterized by a systemic inflammation with variable multiple organ involvement and damage, often including the heart and also the exocrine pancreas.