The purpose of this study was to evaluate and compare the serum proteinogram, identifying and quantifying the acute-phase proteins (APPs) of healthy horses and those naturally affected by colic syndrome. Blood samples were collected from 9 healthy horses and 17 horses with clinical (G1) or surgical (G2) colic at the time of arrival at the veterinary hospital (M0) and 24 (M1), 48 (M2), and 72 (M3) hours after the initiation of treatment. The APPs were separated by polyacrylamide gel electrophoresis (SDS-PAGE), and their concentrations were determined by computerized densitometry. Protein identification was performed using matrix assisted laser desorption/ionization-time of flight mass spectrometry. Nine APPs were identified: α2-macroglobulin, ceruloplasmin, transferrin, albumin, α1-antitrypsin, haptoglobin, α1-acid glycoprotein, apolipoprotein A1, and serum amyloid A. Ceruloplasmin (Cp) presented an elevation at M0 in G2 in relation to G1 and the control group (CG). Serum amyloid A (SAA) presented an elevation with a difference at M3 in G1 and G2, compared with CG. In the comparison between the time points within each group (G1 and G2), there was an increase in SAA in G2 with a difference at M1, M2, and M3. Cp and SAA were suitable for evaluating the acute-phase response in horses with colic. Cp was an indicator of colic with surgical resolution. SAA presented favorable behavior for its use as a biomarker to establish the prognosis in horses with colic. The serial measurement of these proteins was useful in differentiating the clinical or surgical treatment and prognosis of horses with this disorder.