OBJECTIVE Computed tomography (CT)-based attenuation correction (CTAC) in single-photon emission computed tomography (SPECT) is highly accurate, but it requires hybrid SPECT/CT instruments and additional radiation exposure. To obtain attenuation correction (AC) without the need for additional CT images, a deep learning method was used to generate pseudo-CT images has previously been reported, but it is limited because of cross-modality transformation, resulting in misalignment and modality-specific artifacts. This study aimed to develop a deep learning-based approach using non-attenuation-corrected (NAC) images and CTAC-based images for training to yield AC images in brain-perfusion SPECT. This study also investigated whether the proposed approach is superior to conventional Chang's AC (ChangAC). METHODS In total, 236 patients who underwent brain-perfusion SPECT were randomly divided into two groups: the training group (189 patients; 80%) and the test group (47 patients; 20%). Two models were constructed using Autoencoder (AutoencoderAC) and U-Net (U-NetAC), respectively. ChangAC, AutoencoderAC, and U-NetAC approaches were compared with CTAC using qualitative analysis (visual evaluation) and quantitative analysis (normalized mean squared error [NMSE] and the percentage error in each brain region). Statistical analyses were performed using the Wilcoxon signed-rank sum test and Bland-Altman analysis. RESULTS U-NetAC had the highest visual evaluation score. The NMSE results for the U-NetAC were the lowest, followed by AutoencoderAC and ChangAC (P < 0.001). Bland-Altman analysis showed a fixed bias for ChangAC and AutoencoderAC and a proportional bias for ChangAC. ChangAC underestimated counts by 30-40% in all brain regions. AutoencoderAC and U-NetAC produced mean errors of <1% and maximum errors of 3%, respectively. CONCLUSIONS New deep learning-based AC methods for AutoencoderAC and U-NetAC were developed. Their accuracy was higher than that obtained by ChangAC. U-NetAC exhibited higher qualitative and quantitative accuracy than AutoencoderAC. We generated highly accurate AC images directly from NAC images without the need for intermediate pseudo-CT images. To verify our models' generalizability, external validation is required.