AIM: To quantify the severity and frequency of ocular pain in Tibetan plateau patients with dry eye, and to evaluate the related factors affecting ocular pain. METHODS: A retrospective study included 160 cases of dry eye disease (DED) patients who were treated from July 2022 to June 2023. Age, gender, occupation, illness course, anxiety, plateau duration, plateau protection, ocular surface disease index scale (OSDI), break-up time (BUT), Schirmer I test (SIT), conjunctivitis, history of ophthalmic medication, autoimmune disease, the workload of daily near vision range, smoking and overnight stay were obtained via comprehensive ophthalmic assessment, and their duration was followed up. Logistic regression analysis was used to determine the related factors affecting ocular pain. RESULTS: Totally 77.5% (124/160) of DED patients had ocular pain, of which the severity of ocular pain was mild, moderate, and severe in 30.0%, 36.3%, and 11.3% of patients, respectively. Frequency of ocular pain was reported occasional, half the time, frequent, and persistent pain in 19.4%, 36.9%, 16.9%, and 4.4%. OSDI score was 19.67±5.70 (13 to 36), and the level of pain was lowly correlated with OSDI (rs=0.316, P<0.001). Logistic regression showed that in plateau DED patients, increased anxiety led to increased severity and frequency of ocular pain [odds ratio (OR)=3.662, 5.613, 2.387, and 4.870; all P<0.05], professional eye protection and improvement of daily sleep quantity decreased pain (OR=0.307, 0.572, 0.418, and 0.789; all P<0.05), while smoking and general protection of plateau did not affect the severity and frequency of ocular pain (all P>0.05). CONCLUSION: Ocular pain is a common complaint in high-altitude DED patients during the pandemic. Anxiety, eye protection, and adequate sleep during the epidemic period are significantly associated with the severity and frequency of ocular pain in patients with plateau DED, while symptoms of DED have relatively little influence on them.