Surfactant deficiency, poor development of the lung structure and fibrosis as a result of inflammation are thought to play an important role in the development of respiratory distress syndrome in premature calves. Nebulised steroid (fluticasone), bronchodilator (salbutamol) and diuretics (furosemide) can be used in combination alongside standard treatment procedures for premature calves, and might improve viability as observed in infants, foals and horses with pulmonary disorders. Twenty-five premature calves with respiratory distress syndrome were used in this study. Oxygen and supportive treatment were administered to all groups. The first group was used as a control group (Group 1). The nebulised drug combinations were as follows: Group 2: fluticasone + salbutamol, Group 3: salbutamol + furosemide, Group 4: fluticasone + furosemide and Group 5: fluticasone + salbutamol + furosemide. During the 72-h time period of the study, fluticasone (15 μg/kg/12 h), salbutamol (0.025 mg/kg/6 h) and furosemide (1 mg/kg/12h) were applied for 5 min. Arterial blood samples were collected from the auricular artery at 0 h and at 1, 24, 48 and 72 h for blood gas analysis. Significant (P < 0.05) increases in arterial partial oxygen, oxygen saturation and peripheral oxygen saturation and decreases in arterial partial carbon dioxide, lactate and respiration rate were observed in all the nebulised treatment groups, while a statistical difference was observed only for arterial partial carbon dioxide in control group. When comparing the treated groups with the control, it may be concluded that nebulised drugs are highly effective in the therapy of premature calves with respiratory distress syndrome, while the different nebulised groups exhibited similar efficacies.