The effects of combustion with high heat release on the initial instabilities of a mixing layer were investigated experimentally in a two-stream planar mixing layer with hydrocarbon fuels. Experiments were performed with non-premixed reactants Under two distinct conditions where the lean reactant (air) was placed in either the high-speed (AHS) or low-speed stream (FHS) such that the location of heat release was changed relative to the mixing layer. Results show a significantly lengthened instability wavelength and higher growth rate for the AHS case and a reduced spacing and smaller growth rate for the FHS case as compared to non-reacting results. These observed trends in the combustion generated instability qualitatively agree with those predicted by the linear instability analysis of Trouve et al, [12] using a heat release-modified density field. The modified density field causes a higher mixture fraction in the 'internal' mixing layer which supports a relatively stationary reaction zone. As all heat release parameters were kept the same in the AHS and FHS cases, the changes in instability can not be attributed to the dilation or baroclinic torque effects in vorticity reduction, or the increase in viscosity associated with the heat release, but are fundamentally linked to a change in the instability at the splitter plate. Tripped (turbulent) inlet conditions caused no discernable change in the structure of the mixing layer suggesting that the effects of heat release manifest in the instability dominate the mixing behavior of the layer.