Purpose:The aim was to evaluate tear osmolarity of patients with clinically unilateral pseudoexfoliation (PEX) syndrome and to compare the values with otherwise normal subjects. Methods: Sixty-two eyes of 31 patients with unilateral PEX syndrome and 31 eyes of 31 normal subjects were studied. The TearLab osmolarity system (OcuSense, Inc, San Diego, CA, USA) was used to measure tear osmolarity. Eyes were grouped as normal eyes of patients having unilateral PEX syndrome (group A), eyes of patients having unilateral PEX syndrome with deposits of PEX material (group B) and eyes of normal subjects (group C). Differences in tear osmolarity were compared among groups A, B and C. Independent t-tests and paired t-tests were used for statistical analysis. Results: The mean tear osmolarity was 298.7 Ϯ 7.8 mOsm/l (range 285 to 306) in the control group (group C), 306.3 Ϯ 6.6 mOsm/l (range 290 to 314) in the eyes of patients having PEX syndrome with deposits of pseudoexfoliative material (group B) and 301.4 Ϯ 7.1 mOsm/l (range 284 to 305) in the fellow eye of these patients (group A). There was a significant difference between tear osmolarity of groups C and B (independent t-test, p = 0.011). Also, there was a significant difference between the osmolarity of each eye of patients with unilateral PEX syndrome (groups A and B) (paired t-test, p = 0.001). The difference between tear osmolarity of groups A and C was not statistically significant (independent t-test, p = 0.146). Conclusion: In conclusion, tear osmolarity is higher in both eyes of patients when compared with normal subjects, using the independent t-test (although highest in clinically positive eyes of these patients). Both eyes of patients having PEX syndrome could be more prone to the development of dry eye syndrome.