The effect of the application of plasma-activated water (PAW) on the quality and preservation of fresh-cut lettuce is reported in this article. PAW was produced by using a liquid-cathode air discharge. The average (bulk) water temperature was kept at $\sim$ 22 $^{\circ}$ C during the activation procedure and stored at 4 $^{\circ}$ C for up to five days. The pH value, electrical conductivity, and concentrations of H $_{2}$ O $_{2}$ and NO $_{3}^{-}$ in liquid at day 1 were 2.81, 1492 $\mu$ S/cm, and 77.8 and 223.4 mg/L, respectively, with slight variations over the whole storage time. No measurable amounts of NO $_{2}^{-}$ were found. Twenty pieces of lettuce leaves were washed for 1 and 5 min in 1 L of PAW and stored for one and five days. PAW treatments were compared to tap water treatments. The lettuce samples were stored at 4 $^{\circ}$ C and analyzed on days 1, 3, and 7. The chromatic parameter results suggest that PAW treatments significantly reduce the degradation of lettuce chlorophyll from day 3 of refrigerated storage. The lettuce firmness was not significantly modified. The microbiological results of aerobic mesophilic (RAM), enterobacteriaceae, and psychrotrophs populations have shown that lettuce treated with PAW after three days of storage exhibited the strongest inactivation efficiency. Psychrotrophs counts were maintained for up to seven days. Similar inactivation efficiencies were found regardless of the PAW storage time. PAW treatments also favored both the antioxidant capacity FRAP, ABTS, and DPPH, and the total phenolic contents of lettuce at day 7 of storage.