A randomized controlled study was designed to investigate the efficacy of a combined treatment of the Chinese herbal medicine Yin Qiao San and antibiotic medicine (Group B; N = 32) for treating naturally occurring upper respiratory infections in shelter cats, where conventional antibiotic medicine alone was used as the control treatment (Group A; N = 19). A numerical clinical sign scoring system was devised with points given for conjunctivitis, sneezing, nasal discharge, lower respiratory signs, systemic signs and oral cavity involvement. Clinical sign scores for each cat were obtained before treatment and on days 2, 4, 6, 8 and 10 after initiation of treatment. The mean clinical scores of each group on days 2, 4, 6, 8 and 10 were compared to pre-treatment scores using the Wilcoxon signed rank test to determine the significance of clinical sign score reduction. There was no significant reduction in mean clinical sign scores for Group A on Days 2, 4 and 10, but a significant reduction occurred on Days 6 and 8 (p=0.002 and 0.0006, respectively). On the other hand, by Day 4 in Group B there was a significant improvement (p<0.001), and remained significant throughout Days 6, 8 and 10. No adverse effects occurred. The combination of Yin Qiao and Clavamox or doxycycline resulted in faster and more significant clinical improvement of cats with URI than antibiotics alone and was cost effective and had no adverse side effects.