Optical aberrations degrade the performance of fluorescence microscopy. Conventional adaptive optics (AO) leverages specific devices, such as the Shack–Hartmann wavefront sensor and deformable mirror, to measure and correct optical aberrations. However, conventional AO requires either additional hardware or a more complicated imaging procedure, resulting in higher cost or a lower acquisition speed. In this study, we proposed a novel space-frequency encoding network (SFE-Net) that can directly estimate the aberrated point spread functions (PSFs) from biological images, enabling fast optical aberration estimation with high accuracy without engaging extra optics and image acquisition. We showed that with the estimated PSFs, the optical aberration can be computationally removed by the deconvolution algorithm. Furthermore, to fully exploit the benefits of SFE-Net, we incorporated the estimated PSF with neural network architecture design to devise an aberration-aware deep-learning super-resolution model, dubbed SFT-DFCAN. We demonstrated that the combination of SFE-Net and SFT-DFCAN enables instant digital AO and optical aberration-aware super-resolution reconstruction for live-cell imaging.