Methyl alcohol intoxications are characterized by high lethality and high prevalence of serious visual and brain damage in survivors. The mechanisms of toxic brain damage are complex and the role of carbonyl stress has not been studied yet. We measured the acute and follow-up concentrations of reactive carbonyl compounds in patients with acute methyl alcohol intoxication. Blood samples were collected from 28 subjects hospitalized with confirmed methyl alcohol intoxication and from 36 subjects who survived poisoning 2 years after discharge. Serum concentrations of C 6–12 reactive aldehydes were measured by liquid chromatography–electrospray ionization–tandem mass spectrometry. The acute concentrations of all measured reactive aldehydes were higher than the follow-up concentrations: 36.4 ± 4.8 vs. 21.6 ± 5.2 ng cm −3 for C 6 ; 38.9 ± 5 vs. 17.0 ± 2.0 ng cm −3 for C 7 ; 18.8 ± 3.9 vs. 4 ± 0 cm −3 for C 8 ; 36.5 ± 3.9 vs. 19.0 ± 3.0 ng cm −3 for C 9 ; 6.1 ± 0.4 vs. 4.0 ± 0.5 ng cm −3 for C 10 ; 13.6 ± 3.0 vs. 3.7 ± 0.6 ng cm −3 for C 11 ; and 7.8 ± 0.4 vs. 4.7 ± 0.4 ng cm −3 for C 12 (all p  < 0.001). The patients who survived the intoxication had higher concentration of reactive carbonyl compounds than those who died: 38.6 ± 5.9 vs. 28.3 ± 1.7 ng cm −3 for C 6 ( p  = 0.002); 20.7 ± 4.7 vs. 11.8 ± 1.2 ng cm −3 for C 8 ( p  = 0.001); 37.7 ± 4.8 vs. 31.8 ± 3.8 ng cm −3 for C 9 ( p  = 0.042); and 7.9 ± 0.6 vs. 7.3 ± 0.5 ng cm −3 for C 12 ( p  = 0.022). A significant association was present between severity of metabolic acidosis, anion gap, and the acute concentration of measured biomarkers: r  = − 0.39; p  = 0.046 for C 6 ; r  = − 0.42; p  = 0.035 for C 7 ; r  = − 0.48; p  = 0.012 for C 8 ; r  = − 0.39; p  = 0.046 for C 9 ; and r  = − 0.47; p  = 0.015 for C 11 . The acute concentration of C 6 –C 12 reactive aldehydes positively correlated with the acute serum concentration of leukotrienes (all p  < 0.05). Acute elevation of serum concentration of reactive carbonyl compounds suggests that carbonyl stress is involved in the mechanisms of leukotriene-mediated neuroinflammatory response to methyl alcohol-induced toxic brain damage. Graphical abstract