Optical imaging offers a number of advantages over electrophysiology including cell-type specificity. However, its application has been limited to the investigation of shallow brain regions (less than 2 mm) because of the light scattering property of brain tissue. Passive optical conduits, such as graded-index lenses and waveguides, have permitted access to deeper locales but with restricted resolution and field of view, while creating massive lesions along the inserted path. Here we report an implantable complementary metal–oxide–semiconductor fluorescence imager with single-neuron resolution. The imager has a 512-pixel silicon image sensor post-processed into a 4.1-mm-long, 120-μm-wide shank with a collinear fibre for illumination. It can record transient fluorescent signals in deep brain regions at 400 frames per second. We show that the system can offer single-neuron resolution in functional imaging of GCaMP6s-expressing neurons at a frame rate of 400 frames per second.