Background: Surgical stress response is a host defense mechanism against tissue injury but its exaggeration can cause postoperative morbidity. Anaesthetics can modulate this response with variable degrees. Therefore, this study was conducted to compare the immune-modulatory effects of intraoperative intravenous infusion of propofol versus ketamine. Patients and Methods: Forty patients scheduled for open colectomy under inhalational based general anaesthesia were included. They were allocated randomly into Group P (n= 20) which was given intravenous propofol 1% at a subanaesthetic infusion dose of 17μg/kg/min, and group K (n= 20) which was given Ketamine 0.3% (150mg/50ml) at a subanaesthetic infusion dose of 5μg/kg/min. The primary outcome was the post-infusion serum IL-6 2 hours after the start of infusion. The secondary outcomes were IL-1β, TLC, absolute neutrophil count and N/L ratio, glucose level, CRP level, postoperative agitation, mean NRS score for pain at rest and movement during the first day, and time to the resumption of GIT function. Results: Post-infusion serum IL-6 after 2 hours was significantly higher in group K (P<0.001). Additionally, Serum IL-1β, glucose and CRP levels were significantly higher in Group K. Postoperative agitation score was significantly higher (P<0.001) and mean postoperative pain score during rest was significantly lower (P 0.003) in group K. Other outcomes were comparable between both groups. Conclusions: Propofol is more effective than ketamine in reducing the surgical stress response as noted by decreased IL-6 and IL-1β, blood glucose, and CRP when compared with ketamine.