This cross-sectional study aims to verify the relationship between quantitative multivolume proton-magnetic resonance imaging (¹H-MRI) and clinical indicators of ventilatory abnormalities in cystic fibrosis (CF) lung disease.Non-enhanced chest MRI, spirometry and multiple breath washout was performed by 28 patients (10–27 years) with CF lung disease. Images acquired at end-inspiration and end-expiration were registered by optical flow to estimate expiratory–inspiratory proton-density change (Δ¹H-MRI) as a measure of regional ventilation. Magnetic resonance images were also evaluated using a CF-specific scoring system.Biomarkers of CF ventilation impairment were defined from the Δ¹H-MRI as follows: Δ¹H-MRI median, Δ¹H-MRI quartile coefficient of variation (QCV) and percentage of low-ventilation volume (%LVV). Imaging biomarkers correlated to all the clinical measures of ventilation abnormality, with the strongest correlation between Δ¹H-MRI median and forced expiratory volume in 1 s (r²=0.44, p<0.001), Δ¹H-MRI QCV and lung clearance index (LCI) (r²=0.51, p<0.001) and %LVV and LCI (r²=0.66, p<0.001). Correlations were also found between imaging biomarkers of ventilation and morphological scoring.The study showed a significant correlation between quantitative multivolume MRI and clinical indicators of CF lung disease. MRI, as a non-ionising imaging technique, may be particularly attractive in CF care for longitudinal evaluation, providing a new imaging biomarker to detect early ventilatory abnormalities.