The efficiency of polymer – metal oxide hybrid solar cells depends critically on the intimacy of mixing of the two semiconductors. The effect of side chain functionalization on the morphology and performance of conjugated polymer:ZnO solar cells is investigated. Using an ester-functionalized side chain poly(3-hexylthiophene-2,5-diyl) derivative (P3HT-E), the nanoscale morphology of ZnO:polymer solar cells is significantly more intimately mixed compared to ZnO:poly(3-hexylthiophene-2,5-diyl) (ZnO:P3HT), as evidenced experimentally from a 3D reconstruction of the phase separation using electron tomography. Photoinduced absorption reveals nearly quantitative charge generation for the ZnO:P3HT-E blend but not for ZnO:P3HT, consistent with the results obtained from solving the 3D diffusion equation for excitons formed in the polymer within the two experimental ZnO morphologies. For thin ZnO:P3HT-E active layers (∼50 nm) this yields a significant improvement of the solar cell performance. For thicker cells, however, the reduced hole mobility and a reduced percolation of ZnO pathways hinders charge carrier collection, limiting the power conversion efficiency.