Objective To evaluate the performance of a novel magnetic particle-based chemiluminescence reagent for detecting cryptococcal capsular polysaccharide. Methods Serum and cerebrospinal fluid specimens were collected from patients with suspected cryptococcal infection at West China Hospital, Sichuan University between July 2022 and September 2023. All samples were simultaneously tested by chemiluminescence immunoassay (CLIA) and lateral flow immunoassay (LFA), and the results of the two methods were compared. Results A total of 357 patients with suspected cryptococcal infection were enrolled, including 247 serum samples and 110 cerebrospinal fluid samples. The novel magnetic particle-based CLIA reagent exhibited favorable clinical performance for cryptococcal infection detection. For serum and cerebrospinal fluid specimens, the sensitivity was 96.95% and 100.00%, respectively; the specificity was 99.14% and 100.00%, respectively. It showed high consistency with the LFA reagent (the kappa values were both greater than 0.98 for serum and cerebrospinal fluid samples). Moreover, the CLIA reagent enables quantitative measurement for clinical therapeutic monitoring. Conclusion The novel magnetic particle-based CLIA reagent possesses good diagnostic performance and can provide reliable and supportive laboratory evidence for clinical practice in both early diagnosis and therapeutic monitoring.