The invention pertains to a technique for enhancing the resolution of images in light sheet microscopy by adding additional enhanced depth-of-focus optical arrangements and high numerical aperture objective lenses. The technique employs an arrangement of three objective lenses and a processor for combining captured images. The image composition utilizes the greater resolving power of the third high numerical aperture objective lens by imaging the light sheet and enhanced depth-of-focus arrangement resulting in improved overall resolution of the light sheet system. The depth of field arrangement could be a simple oscillation of the third objective, a "layer cake," or cubic phase mask component. Any loss in lateral resolution that results from the depth of field arrangement may be compensated for by deconvolution. In some embodiments, other optics, such as an axicon or annular aperture, can provide extended depth of field.