devices, namely ferromagnetic (FM) spin injectors and detectors and non-ferromagnetic organic medium. When evaluating OSV device performance, magnetoresistance (MR) behavior is an important criterion. [7-11] Undoubtedly, decent MR value is strongly expected for its close proof to long distance spin-conserved transport. Continuous efforts of seeking suitable spin polarizer and transport media fueled the development of OSVs during the past decade. [2-4,11-14] On the other hand, debate on MR signal has never ceased since the first report on organic giant magnetoresistance by Xiong. [7] In general, MR response in a prototype OSV device is considered to be positive, namely device resistance under magnetization antiparallel states is larger than that of parallel states. However, negative (abnormal) MR response in OSVs is increasingly discovered thus must not be fortuity. Consequently, distinguishing the working mechanisms of the negative MR signals becomes an important component of organic spintronics. To date, there are several viewpoints to explain this abnormal spin response: 1) Negative polarization is the most representative also the earliest explanation which is primarily extracted from Julliere tunneling formula. [15-17] That is when spin injector is positively (negatively) polarized, while spin detector is negatively (positively) polarized, the MR behavior is negative. However, such explanation is invalid when injecting Organic spin valves (OSVs) have become an essential building block of next-generation memory devices which focus on spin degree of transporting carriers. Meanwhile, negative magnetoresistance (MR) effect in the OSV devices is increasingly observed which deserves further exploration for the rich spin physics behind. In this work, the negative MR response in ferromagnetic (FM) metal-based OSVs using donor−acceptor (D−A) conjugated polymer based on the naphthalenediimide units as a spacer material is observed. The negative MR effect does not result from negative polarization at spin injection and detection interface as well as tunneling anisotropic magnetoresistance effect, but from the spin transport inside the D−A polymer spacer. Even the stacking sequence of the spin injection and detection electrodes is reversed or changed the polymer coating solvents, the D−A polymer contributed negative MR response still can be observed. For further identifying negative MR origin, the bottom FM metal polarizer is replaced into high-polarization La 0.7 Sr 0.3 MnO 3 thin film, negative MR feature is well reproduced. Based on these points, it is deduced that the spin-orientation reversal inside D−A polymer spacer is the ultimate reason for such negative MR response. The filtering-like spin reversal activity is also in positive proportion to intermolecular interaction.