Purpose To analyze the efficacy of liposomal ozonated oil (Ozonest®) treatment, in patients with blepharitis or blepharoconjunctivitis, in improving the signs and symptoms of the pathology. Methods Exploratory, open-label, prospective, single-arm, pre-post comparative pilot study in usual clinical practice, in 20 patients with blepharitis/blepharoconjunctivitis, receiving treatment with liposomal ozonated oil, one drop in each eye, 4 times a day, for 28 days. Main purpose was to assess whether there was a clinically improvement in the blepharitis specific BLISS questionnaire score. Changes in the 12-item OSDI, in eyelid signs of blepharitis assessed by the physicians were also evaluated among other tests, and there was also a subjective evaluation of the treatment by patients. Results The BLISS score significantly improved from 16.4 before treatment to 11.8 after treatment ( p < 0.05). The OSDI score was also significantly improved from 27.5 before treatment to 20.5 after treatment ( p < 0.05). All tests conducted before and after treatment showed significant improvement ( p < 0.05), except for NIBUT. The treatment received a score of 7 out of 10 by the patients. There were no adverse events in any patient. Conclusion Liposomal ozonated oil treatment showed good efficacy in improving the signs and symptoms of blepharitis/blepharoconjunctivitis, satisfaction of patients, and good safety and tolerability.