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Purpose. Investigation of dry eye and corneal Langerhans cells (LCs) in systemic lupus erythematosus (SLE). Methods. Prospective consecutive case series of 27 SLE patients and 27 control subjects. Dry eye was evaluated by lid-parallel conjunctival folds (LIPCOF), Schirmer test, tear break-up time (TBUT), and ocular surface disease index (OSDI) questionnaire. In vivo investigation of corneal LCs density and morphology (LCM) was performed with confocal corneal microscopy (Heidelberg Retina Tomograph with Rostock Cornea Module). Results. Tear production and stability were pathological in SLE subjects compared to control (Schirmer: 8.45 ± 9.82 mm/5 min versus 11.67 ± 3.21 mm/5 min; TBUT: 6.86 ± 3.53 s versus 11.09 ± 3.37 s). OSDI was significantly greater in SLE patients (25.95 ± 17.92) than in controls (11.06 ± 7.18). Central LC density was greater in SLE patients (43.08 ± 48.67 cell/mm2) than in controls (20.57 ± 21.04 cell/mm2). There was no difference in the peripheral LC density (124.78 ± 165.39 versus 78.00 ± 39.51 cell/mm2). LCM was higher in SLE patients in the centre (1.43 ± 0.79) and in the periphery (2.89 ± 0.42) compared to controls (centre: 1.00 ± 0.69, periphery: 2.35 ± 0.54). Conclusions. Significant changes in dry eye parameters and marked increase of central LCs could be demonstrated in SLE patients. SLE alters not only the LC density but also the morphology, modifies corneal homeostasis, and might contribute to the development of dry eye.