To compare the macular morphology of good and poor responders to eplerenone treatment in chronic central serous chorioretinopathy (CSCR) patients. Thirty eyes of 29 patients with chronic CSCR were treated with 50 mg/day oral eplerenone and followed up for 1 year. The integrity of outer retinal layers at baseline was assessed using optical coherence tomography. Patients who showed complete resolution of subretinal fluid at 1 year were assigned to the good responder group (Group 1), whilst those who showed moderate or no resolution were classified as poor responders (Group 2). Ellipsoid zone interruption, ELM interruption and hyperreflective foci in outer segment (OS) and outer nuclear layer (ON layer) was significantly more frequent in Group 2 than in Group 1 (p < 0.05 for all parameteres). Outer segment elongation was significantly more frequently seen in Group 1 than in Group 2 (p < 0.05) Multivariable regression analysis showed that intact ellipsoid zone at baseline is an independent predictor of good therapeutic response, with an odds ratio of 26.00 (95% CI 3.69–183.45; p = 0.001) after controlling for the effect of hyperreflective foci and ELM integrity. There is higher chance of the resolution of subretinal fluid after eplerenone treatment in CSCR patients with intact outer retinal layers at baseline. Baseline morphologic evaluation of the outer retinal layers on OCT scans can be useful in predicting the response to mineralocorticoid antagonist therapy in these patients.