Returning samples from Mars will require an effective method to assess and select the highest-priority geological materials. The ideal instrument for sample triage would be simple in operation, limited in its demand for resources, and rich in produced diagnostic information. Pyrolysis–Fourier infrared spectroscopy (pyrolysis-FTIR) is a potentially attractive triage instrument that considers both the past habitability of the sample depositional environment and the presence of organic matter that may reflect actual habitation. An important consideration for triage protocols is the sensitivity of the instrumental method. Experimental data indicate pyrolysis-FTIR sensitivities for organic matter at the tens of parts per million level. The mineral matrix in which the organic matter is hosted also has an influence on organic detection. To provide an insight into matrix effects, we mixed well-characterized organic matter with a variety of dry minerals, to represent the various inorganic matrices of Mars samples, prior to analysis. During pyrolysis-FTIR, serpentinites analogous to those on Mars indicative of the Phyllocian Era led to no negative effects on organic matter detection; sulfates analogous to those of the Theiikian Era led, in some instances, to the combustion of organic matter; and palagonites, which may represent samples from the Siderikian Era, led, in some instances, to the chlorination of organic matter. Any negative consequences brought about by these mineral effects can be mitigated by the correct choice of thermal extraction temperature. Our results offer an improved understanding of how pyrolysis-FTIR can perform during sample triage on Mars. Key Words: Mars—Life-detection instruments—Search for Mars’ organics—Biosignatures. Astrobiology 16, 831–845.