This study investigates the changes in mitochondrial DNA (mtDNA) and nuclear DNA (nDNA) levels in the serum of patients with severe polytrauma and their association with the development of infectious pulmonary complications and mortality. The study involved 7 healthy volunteers and 25 patients with severe polytrauma, with an average injury severity score (ISS) of 40.2 ± 9.2. Of these, 16 patients (64%) developed purulent tracheobronchitis and pneumonia, while 5 (20%) died. The levels of mtDNA and nDNA were measured at 12 and 24 hours, and on days 3 and 5–7 after injury using a modified procedure with an external DNA control. The results showed a more than 2.5-fold increase in mtDNA levels in deceased patients compared to survivors (p<0.05), while nDNA levels did not show significant differences. In patients with pneumonia, mtDNA levels were 34 times higher than the reference values within the first 12 hours and continued to rise, whereas in those without pneumonia, mtDNA levels were 17 times higher and then decreased. nDNA levels were significantly higher in patients with pneumonia compared to those without, with a 2555-fold increase in the first 12 hours, while in those without pneumonia, nDNA levels decreased 3-fold. The study concludes that mtDNA and nDNA levels in the serum of polytrauma patients can serve as potential markers for predicting the development of infectious pulmonary complications and mortality. The findings suggest that measuring mtDNA and nDNA within the first 24 hours of hospital admission may be useful for early detection and timely treatment. Further research is needed to explore the potential of these markers in predicting and managing infectious complications in polytrauma patients.This study investigates the changes in mitochondrial DNA (mtDNA) and nuclear DNA (nDNA) levels in the serum of patients with severe polytrauma and their association with the development of infectious pulmonary complications and mortality. The study involved 7 healthy volunteers and 25 patients with severe polytrauma, with an average injury severity score (ISS) of 40.2 ± 9.2. Of these, 16 patients (64%) developed purulent tracheobronchitis and pneumonia, while 5 (20%) died. The levels of mtDNA and nDNA were measured at 12 and 24 hours, and on days 3 and 5–7 after injury using a modified procedure with an external DNA control. The results showed a more than 2.5-fold increase in mtDNA levels in deceased patients compared to survivors (p<0.05), while nDNA levels did not show significant differences. In patients with pneumonia, mtDNA levels were 34 times higher than the reference values within the first 12 hours and continued to rise, whereas in those without pneumonia, mtDNA levels were 17 times higher and then decreased. nDNA levels were significantly higher in patients with pneumonia compared to those without, with a 2555-fold increase in the first 12 hours, while in those without pneumonia, nDNA levels decreased 3-fold. The study concludes that mtDNA and nDNA levels in the serum of polytrauma patients can serve as potential markers for predicting the development of infectious pulmonary complications and mortality. The findings suggest that measuring mtDNA and nDNA within the first 24 hours of hospital admission may be useful for early detection and timely treatment. Further research is needed to explore the potential of these markers in predicting and managing infectious complications in polytrauma patients.