AIM AND PURPOSE: To evaluate the effects of two NSAIDs on corneal sensitivity and ocular surface in Sjögren's syndrome (SS) patients. METHODS: In all, 20 SS patients with epithelial corneal defects, were randomly divided into two groups: group 1 (10 females, age 35-63 years), treated with 0.1% indomethacin, one drop three times a day; group 2 (nine females, one male, age 38-65 years) treated with 0.1% diclofenac, at the same regimen. No systemic NSAIDs were allowed. Use of tear substitute was allowed. Corneal sensitivity, corneal staining, BUT, and ocular discomfort, were evaluated before and after 15, 30 days of treatment and 7 days after NSAID discontinuation. For statistical analysis, the Student's t-test and Mann-Whitney U test were used. RESULTS: Both groups showed at day 30 a statistically significant reduction of corneal sensitivity (P<0.05), although the diclofenac-treated group showed a statistically significant lower sensitivity if compared to the indomethacin-treated group (P<0.05). Corneal fluorescein score showed a statistically significantly worst alteration in group 2, 7 days after the discontinuation of the therapy (P=0.02). The ocular discomfort score was statistically significantly reduced in both groups starting from day 15 (P<0.05). DISCUSSION: The results indicate that NSAIDs can be useful in resolving symptoms of ocular discomfort in SS patients. However, they should be used with caution and under close monitoring, and the treatment should be promptly discontinued if corneal epithelial defects develop or worsen during treatment.