Objective To evaluate the therapeutic effects of low carbohydrate and high fat enteral nutrition (EN) combined with parenteral nutrition (PN) in treatment of patients with chronic obstructive pulmonary disease (COPD) undergoing mechanical ventilation. Methods One hundred and thirteen patients with COPD undergoing mechanical ventilation were randomly divided into treatment group A (n=37), treatment group B (n=37) and control group (n=39), and were managed with low carbohydrate and high fat EN combined with conventional PN treatment, low carbohydrate and high fat EN combined with low carbohydrate and high fat PN treatment, and conventional EN combined with conventional PN treatment, respectively. Parameters of blood gas analysis, respiratory function and blood lipid were measured 1 d before nutrition treatment and 10 d after nutrition treatment, and time of weaning, days of PN and EN, hospitalization days, total cost of hospitalization and cost of nutrition treatment were recorded in each group. Results Ten days after nutrition treatment, the parameters of blood gas analysis and respiratory function in treatment group A and treatment group B were significantly improved compared with control group (P<0.05), and those in treatment group B were significantly improved compared with treatment group A (P<0.05). Ten days after nutrition treatment, the parameters of blood lipid in treatment group A and treatment group B were significantly higher than those in control group (P<0.05), and the parameters of blood lipid in treatment group B were significantly higher than those in treatment group A (P<0.05). The time of weaning, days of PN and EN, hospitalization days, total cost of hospitalization and cost of nutrition treatment in treatment group A and treatment group B were significantly lower than those in control group (P<0.05), and the parameters in treatment group B were significantly lower than those in group A (P<0.05). Conclusion Low carbohydrate and high fat EN combined with conventional PN treatment and low carbohydrate and high fat EN combined with low carbohydrate and high fat PN treatment may yield better therapeutic effects in patients with COPD undergoing mechanical ventilation, and the latter treatment may outperform the former one.