For patients undergoing VATS lobectomy, 1.5 mg/kg esketamine-based PCIA was associated with a good postoperative analgesia, reducing the SF-MPQ score and the levels of IL-6 and TNF-α, improving perioperative depression and the EQ-5D score, and facilitated early postoperative mobilization, without severe AEs observed. Here, IL6 is linked to depressive disorder.