A series of alternating copolymers of cyclopenta[2,1-b;3,4-b′]dithiophene (CPDT) and thieno[3,4-c]pyrrole-4,6-dione (TPD) have been prepared and characterized for polymer solar cell (PSC) applications. Different alkyl side chains, including butyl (Bu), hexyl (He), octyl (Oc), and 2-ethylhexyl (EH), are introduced to the TPD unit in order to adjust the packing of the polymer chain in the solid state, while the hexyl side chain on the CPDT unit remains unchanged to simplify discussion. The polymers in this series have a simple main chain structure and can be synthesized easily, have a narrow band gap and a broad light absorption. The different alkyl chains on the TPD unit not only significantly influence the solubility and chain packing, but also fine tune the energy levels of the polymers. The polymers with Oc or EH group have lower HOMO (highest occupied molecular orbital) and LUMO (lowest unoccupied molecular orbital) energy levels, resulting higher open circuit voltages (Voc) of the PSC devices. Power conversion efficiencies (PCEs) up to 5.5% and 6.4% are obtained from the devices of the Oc substituted polymer (PCPDTTPD-Oc) with PC61BM and PC71BM, respectively. This side chain effect on the PSC performance is related to the formation of a fine bulk heterojunction structure of polymer and PCBM domains, as observed with atomic force microscopy.