Objective: To investigate the effect of dexmedetomidine on stress response and immune balance in patients with acute respiratory distress syndrome(ARDS) undergoing mechanical ventilation. Methods: From March 2016 to September 2018, 90 ARDS patients with mechanical ventilation in Chongqing Three Gorges Center Hospital were randomly divided into dexmedetomidine group(D group, 30 cases), propofol group(P group, 30 cases), midazolam group(M group, 30 cases) by random number table method.Another 30 healthy workers in our hospital were selected as normal control group(C group). In M, P and D groups, the sedative drugs were infused by micro-pump on the basis of analgesic treatment(fentanyl citrate). The heart rate(HR), mean arterial pressure(MAP), Murray score, acute physiology and chronic health evaluation Ⅱ(APACHEⅡ) score, plasma norepinephrine(NS), plasma cortisol(Cor), and blood T lymphocyte subsets(CD₄⁺, CD₈⁺, CD₄⁺/CD₈⁺) were observed in all patients at T0(the beginning of sedation), T1 (6h after sedation), T2 (24h after sedation), T3(48h after sedation). The levels of NS and Cor in plasma and blood T lymphocyte subsets(CD₄⁺, CD₈⁺, CD₄⁺/CD₈⁺) in C group were measured at 8∶00 a. m.the next day. Results: The plasma NS and Cor at T0 in M, P and D group were higher than those in C group (all P<0.05), while the levels of CD₄⁺ were lower than those in C group(all P<0.05). Compared with T0, the plasma NS and Cor decreased at T3 in M, P and D group (all P<0.05). The plasma Cor at T3 in P group was lower than that in M group[(475.77±49.69)μg/L vs.(502.33±60.92)μg/L](t=-26.57, P<0.05). The plasma NS and Cor at T3 in D group were lower than those in M group[(20.64±4.70)ng/L vs.(25.29±4.03)ng/L, (442.83±66.59)μg/L vs.(502.33±60.92)μg/L](t=-4.51, -59.50, all P<0.05), and were lower than those of P group[(20.64±4.70)ng/L vs.(23.60±4.49)ng/L, (442.83±66.59)μg/L vs.(475.77±49.69)μg/L](t=-2.96, -32.93, all P<0.05). Compared with T0, the level of CD₄⁺ decreased at T1, T2 and T3(except T3 in D group) in M, P and D group (all P<0.05), and the level of CD₈⁺ decreased at T1, T2 and T3 in M and P group (all P<0.05), but those in D group at T1, T2 and T3 were not significantly decreased(all P>0.05). The levels of CD₈⁺ at T2 and T3 in P and D groups were higher than that of M group (all P<0.05). The level of CD₄⁺/CD₈⁺ at T3 in D group were higher than that in M and P group[(1.46±0.30) vs.(1.26±0.33), (1.46±0.30) vs.(1.32±0.34)](t=0.21, 0.15, all P<0.05). Conclusion Sedation with dexmedetomidine or propofol can alleviate stress response and improve immune function in ARDS patients undergoing mechanical ventilation, and dexmedetomidine is better than propofol.