PurposeTo develop a deep learning–based approach to reduce the scan time of multipool CEST MRI for Parkinson's disease (PD) while maintaining sufficient prediction accuracy.MethodA deep learning approach based on a modified one‐dimensional U‐Net, termed Z‐spectral compressed sensing (CS), was proposed to recover dense Z‐spectra from sparse ones. The neural network was trained using simulated Z‐spectra generated by the Bloch equation with various parameter settings. Its feasibility and effectiveness were validated through numerical simulations and in vivo rat brain experiments, compared with commonly used linear, pchip, and Lorentzian interpolation methods. The proposed method was applied to detect metabolism‐related changes in the 6‐hydroxydopamine PD model with multipool CEST MRI, including APT, CEST@2 ppm, nuclear Overhauser enhancement, direct saturation, and magnetization transfer, and the prediction performance was evaluated by area under the curve.ResultsThe numerical simulations and in vivo rat‐brain experiments demonstrated that the proposed method could yield superior fidelity in retrieving dense Z‐spectra compared with existing methods. Significant differences were observed in APT, CEST@2 ppm, nuclear Overhauser enhancement, and direct saturation between the striatum regions of wild‐type and PD models, whereas magnetization transfer exhibited no significant difference. Receiver operating characteristic analysis demonstrated that multipool CEST achieved better predictive performance compared with individual pools. Combined with Z‐spectral CS, the scan time of multipool CEST MRI can be reduced to 33% without distinctly compromising prediction accuracy.ConclusionThe integration of Z‐spectral CS with multipool CEST MRI can enhance the prediction accuracy of PD and maintain the scan time within a reasonable range.