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Abstract Spin qubits in gate-defined silicon quantum dots are receiving increased attention thanks to their potential for large-scale quantum computing. Readout of such spin qubits is done most accurately and scalably via Pauli spin blockade (PSB), however, various mechanisms may lift PSB and complicate readout. In this work, we present an experimental study of PSB in a multi-electron low-symmetry double quantum dot (DQD) in silicon nanowires. We report on the observation of non-symmetric PSB, manifesting as blockaded tunneling when the spin is projected to one QD of the pair but as allowed tunneling when the projection is done into the other. By analyzing the interaction of the DQD with a readout resonator, we find that PSB lifting is caused by a large coupling between the different electron spin manifolds of 7.90 μeV and that tunneling is incoherent. Further, magnetospectroscopy of the DQD in 16 charge configurations, enables reconstructing the energy spectrum of the DQD and reveals the lifting mechanism is energy-level selective. Our results indicate enhanced spin-orbit coupling which may enable all-electrical qubit control of electron spins in silicon nanowires.