We aimed to evaluate interleukin-6 (IL-6) tear concentration and clinical outcome in patients with moderate-to-severe bacterial corneal ulcers post corneal collagen cross-linking (CXL) therapy. This pre-post designed study involving 21 moderate-to-severe corneal ulcer patients who underwent CXL therapy. Patients with infectious corneal ulcer were given CXL therapy as adjunctive treatment after 5d of broadspectrum antibiotic treatment. Patients with moderate to severe infectious bacterial corneal ulcers were included in this study. Tear sampling was performed before CXL therapy, using sterile Schimer paper from conjunctival inferior fornix. CXL therapy was performed in accordance with the CXL Dresden protocol. Data recording and tear sampling were then performed at day 1 and day 7 after CXL therapy. Data recording included, presence of conjunctival hyperemia, visual analogue scale (VAS), size of corneal defects, and decemetocele. There was a decrease in IL-6 tear concentration by day 7 after CXL therapy (P=0.001). IL-6 concentration at 1h after therapy (2274.67±2120.46 pg/mL) tended to be lower than before therapy (4330.09±3169.70 pg/mL), but the difference was not statistically significant (P=0.821). The size of corneal defects decreased significantly post CXL (P=0.007). The logMAR visual acuity before and after CXL therapy was not found to be significantly different (P=0.277). There was a significant decrease in VAS values (P=0.018) and blepharospasm (P=0.011) pre and post CXL. There was no significant decrease in conjunctival hyperemia pre and post CXL (P=0.293). There was significant reduction in IL-6 tear concentration and clinical improvement in moderate-to-severe bacterial corneal ulcers which underwent CXL therapy.