Objective: Antiphospholipid antibodies are a group of heterogeneous autoantibodies which have been reported in systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS) in association with thrombosis, fetal loss, and thrombocytopenia. In this study, we aimed to reveal the prevalence and correlation of IgG, IgA, and IgM isotypes of antibodies to cardiolipin (aCL) and antiphosphatidylserine (aPS) with clinical and laboratory manifestations of SLE patients. Methods: Fifty-nine SLE patients and 41 healthy controls were included. Fifteen of patients (25.4%) had secondary APS. aCL and aPS antibody assays were performed by enzyme-linked immunosorbent assay. Results: All isotypes of aCL and aPS antibodies except IgG were higher in patients with or without APS than those in the healthy controls (p < 0.001). The most significant associations were found among migraine and IgA aCL (p < 0.001), livedo reticularis and both IgM aCL and IgM aPS (p < 0.001), migraine and IgM aCL (p < 0.01), pulmonary involvement and IgM aCL (p < 0.01), migraine and IgA aPS (p < 0.01), and both thrombosis and migraine with IgM aPS (p < 0.01). Conclusion: A relatively high prevalence of aCL and aPS antibodies was found in our SLE patients. It seems that isotypes of IgM aCL, IgM aPS, IgA aCL, and IgA aPS antibodies are correlated well with migraine and IgM aPS with thrombosis in SLE patients with secondary APS. The assessment of both IgM and IgA isotypes of aPS and aCL antibodies may be helpful in predicting these manifestations.