Summary Background The carbohydrate alpha‐gal epitope is present in many animal proteins, including those of red meat and animal immunoglobulins, such as cat IgA. Systemic anaphylaxis to the alpha‐gal epitope has recently been described. Objective To investigate and compare the prevalence of alpha‐gal‐specific (s)IgE and its associated factors in the general adult population from two separated (Northern and Southern) European regions (Denmark and Spain, respectively). Methods Cross‐sectional study of 2297 and 444 randomly selected adults from 11 municipalities in Denmark and one in Spain. Alpha‐gal sIgE was assessed by ImmunoCAP to bovine thyroglobulin. Additional assessments included a panel of skin prick test (SPT) to common aeroallergens and epidemiological factors, including the history of tick bites in the Danish series. Results The prevalence of positive (≥ 0.1 kUA/L) sIgE to alpha‐gal was 5.5% and 8.1% in the Danish and Spanish series, respectively. The prevalence of sIgE ≥ 0.35 kUA/L was 1.8% and 2.2% in Denmark and Spain, respectively. Alpha‐gal sIgE positivity was associated with pet ownership in both series and, particularly, cat ownership (data available in the Danish series). Alpha‐gal sIgE positivity was associated with atopy (SPT positivity) in both series, although it was not associated with SPT positivity to cat or dog dander. Alpha‐gal sIgE positivity was strongly associated with a history of tick bites. Conclusions and Clinical Relevance The prevalence of alpha‐gal sIgE antibodies in these general adult European populations is similarly low. The presence of alpha‐gal sIgE antibodies is associated with a history of tick bites, atopy, and cat ownership.