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RATIONALE In patients with asthma, x-ray computed tomography (CT) has provided evidence of thickened airway walls and airway occlusions, but the total number of CT-visible airways and its relationship with disease severity is unknown. OBJECTIVES To measure CT total-airway-count (TAC) in asthma and evaluate relationships with asthma severity, airway morphology, pulmonary function and magnetic-resonance-imaging (MRI) ventilation. METHODS Participants underwent post-bronchodilator inspiratory CT, and pre- and post-bronchodilator spirometry and hyperpolarized 3He MRI. CT TAC was quantified as the sum of airways in the segmented airway-tree, and airway wall-area-percent (WA%) and lumen-area (LA) were measured. MRI ventilation abnormalities were quantified as the ventilation-defect-percent (VDP). MEASUREMENTS AND MAIN RESULTS We evaluated 70 participants including 15 Global-Initiative-for-Asthma (GINA) steps 1-3, 19 GINA4 and 36 GINA5 asthmatics. As compared with GINA1-3, TAC was significantly diminished in GINA4 (p=0.03) and GINA5 (p=0.045). Terminal airway intraluminal occlusion was present in five (two GINA4, three GINA5) of 70 participants. Sub-subsegmental airways were CT-invisible or missing in 69/70 participants; the most common number of missing sub-subsegments was 10. Participants with ≥10 missing subsegments had worse WA% (p<0.0001), LA (p<0.0001) and VDP (p=0.03) than those with <10 missing subsegments. In a multivariable-model, TAC (β=0.50, p=0.001) independently predicted FEV1 (R2=0.27, p=0.003) and in a separate model, TAC (β=-0.53, p<0.0001) independently predicted airway WA% (R2=0.32, p=0.0001). CONCLUSIONS TAC was significantly diminished in participants with greater asthma severity and was related to airway wall thickness and ventilation-defects. Fewer airways in severe as compared with mild asthma challenges our understanding of airways-disease in asthma. Clinical trial registration available at www.clinicaltrials.gov, ID: NCT02351141.