We study the problem of deconvolution for light-sheet microscopy, where the data is corrupted by spatially varying blur and a combination of Poisson and Gaussian noise. The spatial variation of the point spread function of a light-sheet microscope is determined by the interaction between the excitation sheet and the detection objective PSF. We introduce a model of the image formation process that incorporates this interaction and we formulate a variational model that accounts for the combination of Poisson and Gaussian noise through a data fidelity term consisting of the infimal convolution of the single noise fidelities, first introduced in L. Calatroni et al. (SIAM J Imaging Sci 10(3):1196–1233, 2017). We establish convergence rates and a discrepancy principle for the infimal convolution fidelity and the inverse problem is solved by applying the primal–dual hybrid gradient (PDHG) algorithm in a novel way. Numerical experiments performed on simulated and real data show superior reconstruction results in comparison with other methods.