Magnetic anisotropy plays an important role in determining the magnetic functionality of thin film based electronic devices. We present here, the first systematic study of the correlation between magnetoresistance (MR) response in organic spin valves (OSVs) and magnetic anisotropy of the bottom ferromagnetic electrode over a wide temperature range (10 K–350 K). The magnetic anisotropy of a La0.67Sr0.33MnO3 (LSMO) film epitaxially grown on a SrTiO3 (STO) substrate was manipulated by reducing film thickness from 200 nm to 20 nm. Substrate-induced compressive strain was shown to drastically increase the bulk in-plane magnetic anisotropy when the LSMO became thinner. In contrast, the MR response of LSMO/OSC/Co OSVs for many organic semiconductors (OSCs) does not depend on either the in-plane magnetic anisotropy of the LSMO electrodes or their bulk magnetization. All the studied OSV devices show a similar temperature dependence of MR, indicating a similar temperature-dependent spinterface effect irrespective of LSMO thickness, resulting from the orbital hybridization of carriers at the OSC/LSMO interface.