- Summary Background There is no currently no information regarding the role of α-defensins in the pathophysiology of atopic dermatitis (AD). Aim To investigate levels of plasma α-defensins at exacerbation and remission of AD, and to assess their association with clinical severity of AD. Methods Patients with AD during exacerbation were recruited from the Dermatology department at the Chita Medical Academy (Chita, Russian Federation). SCORAD (SCORing Atopic Dermatitis), itch intensity, plasma concentrations of α-defensins, and serum total IgE, interleukin (IL)-1β, IL-8 and IL-10 levels were measured at study entry and after 4 months. Results In total, 82 patients with AD [35 (45.1%) female and 47 (54.9%) male patients, mean ± SD age 42.2 ± 11.5 years, range 15–40] and 30 healthy controls (HCs) were included. Mean objective SCORAD score was 48.8 ± 19.4 and 16.1 ± 8.3 during AD during exacerbation and remission, respectively (P < 0.01). Plasma α-defensin levels in patients with AD (1.41 ± 0.32 μg/L) were significantly higher than in HCs (0.91 ± 0.34 μg/L) (P < 0.001). Significant correlations were found between plasma α-defensin levels with objective SCORAD (r = 0.55, P < 0.001), itch severity (r = 0.25, P < 0.05) and serum IgE levels (r = 0.38, P < 0.001) during AD exacerbation. Serum concentrations of IL-1β, IL-4 and IL-8 were significantly higher and levels of IL-10 were lower at AD exacerbation in patients than in HCs, with a weak negative correlation between plasma α-defensin and serum IL-10 levels (r = −0.22; P < 0.05). Conclusion During AD exacerbation, plasma α-defensin levels are elevated, and are positively correlated with AD clinical severity, itch intensity and serum IgE levels.