Background: Respiratory failure is a common complication of poisoning with significant morbidity and mortality. Mechanical ventilation is life saving. Weaning is the process of liberating patient from mechanical ventilatory support. Interleukin-6 (IL-6) and C-reactive protein (CRP) are inflammatory mediators, released in response to many stressful conditions as weaning from mechanical ventilation. 
Aim of the work: The aim of the study was to assess the role of serum (IL6) level and (CRP) as predictors of outcome of weaning from mechanical ventilation in acutely intoxicated patients admitted to the Poison Control Center– Ain Shams University Hospitals (PCC-ASUHs). And to assess their role in selection of the most appropriate mode for weaning by comparing weaning by pressure support ventilation (PSV) mode, synchronized intermittent mandatory ventilation (SIMV) mode and weaning by the once-daily trial of spontaneous breathing trial by using (T-piece). 
Patients and Methods: The study included 58 acutely intoxicated patients, intubated and mechanically ventilated, admitted to the Intensive Care Unit (ICU) of PCC-ASUHs during the period from May 2016 till September 2018. Patients were categorized consecutively according to the outcome of the 2-hour of spontaneous breathing trial (SBT) into 2 groups: Group I (The SBT Success group): included 19 patients who succeed spontaneous breathing trial. Group II (The SBT failed group): included 39 patients who failed SBT which was further subdivided into 3 groups according to the method of weaning: group (1) PSV group, group (2) SIMV group and group (3) Once T-piece group, each group including 13 patients. Results: IL-6 was significantly increased after 2 days in patients who failed the SBT compared to the success group, while CRP was significantly higher in the failed group during weaning trial and 2 days after. There is no significant difference between the three weaning modes regarding IL6 and CRP. Conclusion: Patients who failed the SBT presented higher inflammatory parameters than those who passed. CRP could predict the outcome of weaning from mechanical ventilation.