During the acute stage of central serous chorioretinopathy (CSC) with retinal elevation, the spectral domain optical coherence tomography (SD-OCT) estimate of ganglion cell layer complex thickness is reduced. Thickness returns to normal after resolution of the event. Measurement error is at least partially responsible for this effect. The reduction in ganglion cell layer complex thickness does not represent atrophy and is not predictive of a poor outcome. We investigated the effects of serous retinal detachment on the ganglion cell layer complex analysis (GCA) by SD-OCT in CSC patients during the acute episodes and after resolution of fluid. We retrospectively reviewed medical records of 30 patients who visited the hospital with a first episode of CSC. We analyzed GCA maps using SD-OCT (Cirrus; Carl Zeiss Meditec, Dublin, CA) at the initial visit with serous retinal elevation and after the absorption of subretinal fluid. For repeatability analysis, we used the intraclass correlation and repeatability coefficient from two consecutive measurements 5 minutes apart in 12 patients. At the initial visit, an average thickness of ganglion cell layer complex was thinner than that measured in the fellow eye (67.4 ± 27.4 μm), but after the absorption of subretinal fluid, it normalized to 87.0 ± 6.7 μm; the difference was statistically significant. The intraclass correlation and repeatability coefficient were low during the period of serous elevation but normalized after fluid resorption. Abnormalities of GCA resulted from the segmentation error of ganglion cell layer and inner plexiform layer during the acute phase of CSC. Serous retinal detachment can affect the GCA and repeatability measurements of the GCA. Clinicians should consider this finding when using the GCA measurement in the diagnosis and management of the patients with retinal contour changes such as retinal elevation including CSC.