Background Simultaneous cytological and metabolic investigation of the pleural effusion provides clinically relevant information about the type and intensity of immune response in the pleural cavity. Methods We investigated 1329 pleural effusions from patients with different pathological changes in the pleural cavity. Evaluated parameters were differential cell count of neutrophils, eosinophils, lymphocytes and monocytes, and values of the coefficient of energy balance. Results We found the lowest numbers of cells and the highest coefficient of energy balance values in patients with heart failure and sepsis; relatively high frequency of eosinophils and slightly decreased coefficient of energy balance values in patients with pneumothorax and haemothorax; the predominance of lymphocytes and low coefficient of energy balance values in patients with tuberculous pleuritis; the predominance of neutrophils and variable coefficient of energy balance values in patients after chest surgery; the highest presence of neutrophils and very low coefficient of energy balance values in patients with chest empyema and the predominance of lymphocytes and normal to low coefficient of energy balance values in patients with pleural malignancy. Conclusions Our findings in patients with heart failure and sepsis suggest the absence of inflammation in the pleural cavity. We observed the manifestation of tissue repair in patients with pneumothorax and haemothorax. Patients with tuberculous pleuritis were predominantly characterized by T cell-driven immune response and oxidative burst of macrophages. We found different intensities of immune responses to the chest surgery. The typical finding in patients with empyema was oxidative burst of neutrophils. In patients with pleural malignancy, weak cytotoxic inflammation predominates together with the intensive inflammation characterized by oxidative burst of macrophages.