This study introduces a new method for identifying COVID-19 infections using blood test data as part of an anomaly detection problem by combining the kernel principal component analysis (KPCA) and one-class support vector machine (OCSVM). This approach aims to differentiate healthy individuals from those infected with COVID-19 using blood test samples. The KPCA model is used to identify nonlinear patterns in the data, and the OCSVM is used to detect abnormal features. This approach is semi-supervised as it uses unlabeled data during training and only requires data from healthy cases. The method’s performance was tested using two sets of blood test samples from hospitals in Brazil and Italy. Compared to other semi-supervised models, such as KPCA-based isolation forest (iForest), local outlier factor (LOF), elliptical envelope (EE) schemes, independent component analysis (ICA), and PCA-based OCSVM, the proposed KPCA-OSVM approach achieved enhanced discrimination performance for detecting potential COVID-19 infections. For the two COVID-19 blood test datasets that were considered, the proposed approach attained an AUC (area under the receiver operating characteristic curve) of 0.99, indicating a high accuracy level in distinguishing between positive and negative samples based on the test results. The study suggests that this approach is a promising solution for detecting COVID-19 infections without labeled data.