To meet the increasing need for low-cost, compact imaging technology with cellular resolution, we have developed a microLED-based structured light sheet microscope for three-dimensional ex vivo and in vivo imaging of biological tissue in multiple modalities. All the illumination structure is generated directly at the microLED panel—which serves as the source—so light sheet scanning and modulation is completely digital, yielding a system that is simpler and less prone to error than previously reported methods. Volumetric images with optical sectioning are thus achieved in an inexpensive, compact form factor without any moving parts. We demonstrate the unique properties and general applicability of our technique by ex vivo imaging of porcine and murine tissue from the gastrointestinal tract, kidney, and brain.