Purpose The aim of this study was to examine the effects of long-term use of hydroxychloroquine (HQ) on the pachymetric, aberrometric, and densitometric values of the cornea and corneal endothelium in lupus patients. Method Twenty-two eyes (study group) of 22 patients using HQ for treatment of lupus and 25 eyes (control group) of 25 healthy individuals were included in this prospective study. A specular microscopy was used to measure corneal endothelial cell density (ECD), percentage of hexagonal cells (HEX%), coefficient of variation of the cell size (CV). Then, a Pentacam® HR corneal tomography system was used to measure central corneal thickness (CCT), corneal aberrometry values in 6-mm pupil diameters and corneal densitometry values in 6-mm corneal zones (0–2 mm and 2–6 mm). Results While ECD was significantly lower in the study group than in the control group (p = 0.034), CCT was significantly higher in the study group (p = 0.032). The higher-order aberrations values and the anterior corneal densitometry values in the 0–2 mm and 2–6 mm corneal zones in the study group were found to be significantly higher than the control group (p = 0.021, p = 0.007 and p = 0.013). Conclusion Prolonged use of HQ may cause some changes in the cornea. In the follow-up of these cases, detailed examination of the cornea as well as the macula may be important for the protection of corneal health.