To evaluate the role of central subfield thickness (CST), cube average thickness (CAT), and cube volume (CV) as imaging biomarkers for severity of diabetic retinopathy within the ETDRS-based grades of retinopathy using spectral domain optical coherence tomography (SD-OCT). This study aims to evaluate the role of macular CST, CAT, and CV on SD-OCT as imaging biomarkers for severity of DR. One hundred ninety-four consecutive cases of type 2 diabetes mellitus were divided according to ETDRS classification: diabetes mellitus without retinopathy (No DR; n = 65), nonproliferative diabetic retinopathy (NPDR; n = 66), and proliferative diabetic retinopathy (PDR; n = 63). Sixty-three healthy controls were included. CST, CAT, and CV were analyzed using SD-OCT. Data were analyzed statistically. Analysis of variance revealed a significant increase in levels of CST, CAT, CV, and LogMAR visual acuity with the increase in severity of DR. Independent t-test revealed significant difference in CST, CAT, and CV between cases with DME and cases without DME. On multivariate linear regression analysis, increase in CST, CAT, and CV were found to indicate the increase in severity of DR. SD-OCT-based imaging biomarkers CST, CAT, and CV are effective tools for documenting the severity of diabetic retinopathy. These imaging biomarkers serve as significant indicators of severity of disease.