This study is a report on combinational effects between four sesquiterpene lactones (SLs) from bay laurel (Laurus nobilis) leaves, and oxytetracycline (OTC) or amoxicillin (AMX) against four fish pathogenic bacteria such as Vibrio anguillarum, V. harveyi, Edwardsiella tarda, and Streptococcus iniae. Individually, four SLs exerted little antibacterial activity against fish pathogenic bacteria. However, when combined with OTC or AMX, they showed synergistic interaction against pathogenic bacteria. Especailly, zaluzanin C (1) reduced the MIC of OTC (or AMX) eight-fold. Our results showed that combinations of SLs with antibiotics (ABTs) are more effective than ABTs alone to control pathogenic bacteria. The highest synergistic effect was observed when zaluzanin C (1) was combined with OTC or AMX against V. harvey or S. iniae, displaying significant reductions of MICs up to 8-fold (0.125 to 0.015?μg/mL and 0.0078 to 0.0009 μg/mL). In addition, zaluzanin C (1) improved the antibiotic potency of OTC against OTC resistant V. harveyi (250?μg/mL to 62.5?μg/mL). Synergism between ABTs and phytochemical such as SLs could be a therapeutically helpful concept to improve the efficacy of ABTs and prevent antibiotic resistance. These results suggest that SLs can be used as an alternative to reduce...