Soil samples from the hyper-arid region in the Atacama Desert in Southern Peru (La Joya Desert) were analyzed for total and labile organic carbon (TOC and LOC), phospholipid fatty acids (PLFA), quantitative real time polymerase chain reaction (qRT-PCR), 4′,6-diamidino-2-phenylindole (DAPI)-fluorescent microscopy, culturable microorganisms, and oxidant activity, to understand the relationship between the presence of organic matter and microorganisms in these types of soils. TOC content levels were similar to the labile pool of carbon suggesting the absence of recalcitrant carbon in these soils. LOC ranged between 2 to 60 µg/g of soil. PLFA analysis indicated a maximum of 2.3 × 105 cell equivalents/g. Culturing of soil extracts yielded 1.1 × 102–3.7 × 103 CFU/g. qRT-PCR showed between 1.0 × 102 and 8 × 103 cells/g; and DAPI fluorescent staining indicated bacteria counts up to 5 × 104 cells/g. Arid and semiarid samples (controls) showed values between 107 and 1011 cells/g with all of the methods used. Importantly, the concentration of microorganisms in hyper-arid soils did not show any correlation with the organic carbon content; however, there was a significant dependence on the oxidant activity present in these soil samples evaluated as the capacity to decompose sodium formate in 10 hours. We suggest that the analysis of oxidant activity could be a useful indicator of the microbial habitability in hyper-arid soils, obviating the need to measure water activity over time. This approach could be useful in astrobiological studies on other worlds.