In this paper we discuss the L-p-L-q boundedness of both spectral and Fourier multipliers on general locally compact separable unimodular groups G for the range 1 < p <= 2 <= q < infinity. As a consequence of the established Fourier multiplier theorem we also derive a spectral multiplier theorem on general locally compact separable unimodular groups. We then apply it to obtain embedding theorems as well as time-asymptotics for the L-p-L-q norms of the heat kernels for general positive unbounded invariant operators on G. We illustrate the obtained results for sub-Laplacians on compact Lie groups and on the Heisenberg group, as well as for higher order operators. We show that our results imply the known results for L-p-L-q multipliers such as Hormander's Fourier multiplier theorem on R-n or known results for Fourier multipliers on compact Lie groups. The new approach developed in this paper relies on advancing the analysis in the group von Neumann algebra and its application to the derivation of the desired multiplier theorems.