Abstract: Objective To discuss the application of micro-Raman confocal system in the test of serum sample of coronary heart disease (CHD). Methods The serum samples of 46 patients with coronary heart disease confirmed by coronary angiography and 50 subjects receiving healthy physical examination were selected in the First Affiliated Hospital of Army Medical University between August 2018 and January 2019. The XploRA PLUS automatic microscopic confocal Raman system was used to measure and analyze the Raman spectrum of serum. Statistical processing was performed by orthogonal partial least squares discriminant analysis (OPLS-DA) by using SIMCA-P14.1 analysis software. Results The Raman spectrum mean peak of the two groups was similar; At the displacement of 1 080.47/cm, 1 102.01/cm, 1 127.52/cm, 1 335.46/cm, 1 603.83/cm, 1 657.69/cm, the vibration intensity of the CHD group was higher than that of the control group, At the displacement of 1 154.51/cm, 1 516.81/cm, the vibration intensity results were just the opposite. The changes of these spectral peaks may be beneficial to the screening of CHD by Raman spectra; R²X (cum) of the OPLS-DA model was 0.881, R²Y (Cum) was 0.644, the predictability of the model Q² (cum) was 0.497, and the AUC based on OPLS-DA were 0.970 and 0.970, respectively. Conclusion The microscopic confocal Raman system combined with OPLS-DA analysis can quickly and conveniently distinguish the serum samples from the known coronary heart disease group and the healthy group, providing a new possibility for the detection and diagnosis of coronary heart disease as an exploratory experimental method.