Objective To investigate the clinical value of serum total immunoglobulin E (IgE), specific IgE (sIgE), C-reactive protein (CRP) and interleukin-6 (IL-6) in the diagnosis of acute urticaria. Methods A total of 43 patients with acute urticaria admitted to our hospital from June 2022 to April 2023 were selected as the acute urticaria group, and 43 healthy members in the same period were selected as the control group. The levels of serum total IgE, sIgE, CRP and IL-6 were detected and compared between the two groups. Results The serum total IgE level in the acute urticaria group was (178.35±64.29) kU/L, which was higher than (86.42±30.57) kU/L in the control group, the difference was statistically significant (P <0.05). The levels of house dust mites, food allergens, animal dander, and mold sIgE in the acute urticaria group were higher than those in the control group, the difference was statistically significant (P <0.05). The levels of CRP and IL-6 in the acute urticaria group were higher than those in the control group, the difference was statistically significant (P <0.05). Conclusion Serum total IgE, sIgE, CRP and IL-6 have important clinical value in the diagnosis of acute urticaria. The detection of biomarkers is helpful for clinicians to diagnose acute urticaria more accurately and provide more accurate treatment guidance for patients.