Background Babesia canis infection induces a marked acute phase response (APR) that might be associated with alteration in lipid and lipoprotein metabolism and disease prognosis. Hypothesis Dogs with B. canis ‐induced APR develop dyslipidemia with altered lipoprotein concentration and morphology. Animals Twenty‐nine client‐owned dogs with acute B. canis infection and 10 clinically healthy control dogs. Methods Observational cross‐sectional study. Serum amyloid A (SAA) was measured using ELISA. Cholesterol, phospholipids, and triglycerides were determined biochemically. Lipoproteins were separated using agarose gel electrophoresis. Lipoprotein diameter was assessed by polyacrylamide gradient gel electrophoresis; correlation with ApoA‐1 (radioimmunoassay) and SAA was determined. Results Dogs with B. canis infection had a marked APR (median SAA, 168.3 μg/mL; range, 98.1‐716.2 μg/mL) compared with controls (3.2 μg/mL, 2.0‐4.2 μg/mL) ( P < .001). Dogs with B. canis infection had significantly lower median cholesterol (4.79 mmol/L, 1.89‐7.64 mmol/L versus 6.15 mmol/L, 4.2‐7.4 mmol/L) ( P = .02), phospholipid (4.64 mmol/L, 2.6‐6.6 mmol/L versus 5.72 mmol/L, 4.68‐7.0 mmol/L) ( P = .02), and α‐lipoproteins (77.5%, 27.7%‐93.5% versus 89.2%, 75.1%‐93.5%) ( P = .04), and higher ApoA‐1 (1.36 U, 0.8‐2.56 U versus 0.95 U, 0.73‐1.54 U) concentrations ( P = .02). Serum amyloid A correlated with high‐density lipoproteins (HDLs) diameter (rho = .43; P = .03) and ApoA‐1 (rho = .63, P < .001). Conclusions and Clinical Importance Major changes associated with B. canis ‐induced APR in dogs are related to concentration, composition, and morphology of HDL particles pointing to an altered reverse cholesterol transport. Parallel ApoA‐1 and SAA concentration increase is a unique still unexplained pathophysiological finding.

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