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Introduction: The most clinically useful concept in asthma is based on the intensity of treatment required to achieve good asthma control. Biomarkers to guide therapy are needed. Aims: To investigate the role of circulating levels of soluble urokinase plasminogen activator receptor suPAR as a marker for asthma severity. Methods: We recruited patients evaluated at the Asthma Clinic, University of Thessaly, Greece. Asthma severity and control were defined according to the GINA strategy and Asthma Contro Test (ACT). Anthropometrics, spirometry, fractional exhaled nitric oxide (FeNO), suPAR, blood cell count, c-reactive protein (CRP), and analyses of kidney and liver function were obtained. Patients with a history of inflammatory, infectious, or malignant disease or other lung disease, more than 5 pack years of smoking history, or corticosteroid therapy were excluded. Results: We evaluated 74 asthma patients (69% female, mean age 57 ± 17 years, mean body mass index (BMI) 29 ± 6 kg/m2). In total, 24%, 13%, 6%, 5%, 29% and 23% of the participants had mild well-controlled, mild uncontrolled, moderate well-controlled, moderate uncontrolled, severe well-controlled, and severe uncontrolled asthma, respectively. Overall, 67% had T2-high asthma, 26% received biologics (15% and 85% received omalizumab and mepolizumab, respectively), and 34% had persistent airway obstruction. suPAR levels were significantly lower in asthmatics with moderate uncontrolled asthma than in patients with severe uncontrolled asthma without (2.1 ± 0.4 vs. 3.3 ± 0.7 ng/mL, p = 0.023) or with biologics (2.1 ± 0.4 vs. 3.6 ± 0.8 ng/mL, p = 0.029). No correlations were found between suPAR levels and age, BMI, T2 biomarkers, CRP, or spirometric parameters. Conclusions: suPAR levels were higher in asthmatics with severe disease than in those with moderate uncontrolled asthma.