We　report　a　systematic　study　of　the　efficiency　limitations　of　non-fullerene　organic　solar　cells　that　exhibit　a　small　energy　loss　(E-loss)　between　the　polymer　donor　and　the　non-fullerene　acceptor.　To　clarify　the　impact　of　Eloss　on　the　performance　of　the　solar　cells,　three　thieno[3,4-c]　pyrrole-4,6-dione-based　conjugated　polymers　(PTPD3T,　PTPD2T,　and　PTPDBDT)　are　employed　as　the　electron　donor,　which　all　have　complementary　absorption　spectra　compared　with　the　ITIC　acceptor.　The　corresponding　photovoltaic　devices　show　that　low　Eloss　(0.54　eV)　in　PTPDBDT:　ITIC　leads　to　a　high　open-circuit　voltage　(Voc)　of　1.05　V,　but　also　to　a　small　quantum　efficiency,　and　in　turn　photocurrent.　The　high　Voc　or　small　energy　loss　in　the　PTPDBDT-based　solar　cells　is　a　consequence　of　less　non-radiative　recombination,　whereas　the　low　quantum　efficiency　is　attributed　to　the　unfavorable　micro-phase　separation,　as　confirmed　by　the　steady-state　and　time-resolved　photoluminescence　experiments,　grazing-incidence　wide-angle　X-ray　scattering,　and　resonant　soft　X-ray　scattering　(R-SoXS)　measurements.　We　conclude　that　to　achieve　high　performance　non-fullerene　solar　cells,　it　is　essential　to　realize　a　large　Voc　with　small　Eloss　while　simultaneously　maintaining　a　high　quantum　efficiency　by　manipulating　the　molecular　interaction　in　the　bulk-heterojunction.