Background Atopic dermatitis (AD) is a common chronic skin disease with an inflammatory pathophysiology that includes the activation of the innate and adaptive immune systems. Objectives We aimed to investigate the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), eosinophil-to-lymphocyte ratio (ELR) and eosinophil-to-neutrophil ratio (ENR) in AD patients, according to age and disease severity. Methods This is a retrospective, population-based cohort study conducted between the years 2005 and 2020, comparing hematological markers of AD patients and sex-age-ethnicity matched controls. AD patients were further divided by age and disease severity (mild, moderate-to-severe AD). We created a decision tree to predict moderate-severe AD. Results A total of 13,928 patients with AD were included in this study: 6,828 adults and 7,100 children, with 13,548 controls. NLR, PLR, and ELR were lower in children compared to adults (p-values < 0.001). NLR, PLR, ELR, and ENR were increased in moderate-severe AD patients compared to mild AD patients (p-values < 0.001). PLR, ELR, and ENR were increased in AD patients versus controls (p-values < 0.001), with an additional increase in the NLR of moderate-to-severe AD patients. Patients with an ELR < 0.21, a PLR > 161, and ENR 0.016 should be considered high risk for developing severe AD, as well as patients with an ELR > 0.21 and age at diagnosis < 30 or age > 30 years and Mean Platelet Volume (MPV) 9. Conclusion Hematological ratios were significantly higher in moderate-to-severe AD patients, compared to mild AD patients. Hematological markers were lower in children with AD compared to adults, except for ENR, likely reflecting age-related changes in blood count parameters. These markers can assist in the management and follow-up of AD patients.