The genomes of the Asgard superphylum of Archaea hold clues pertaining to the nature of the host cell that acquired the mitochondrion at the origin of eukaryotes 1-4 . Representatives of the Asgard candidate phylum Candidatus Lokiarchaeota (Lokiarchaeon) have the capacity for acetogenesis and fermentation 5-7 , but how their metabolic activity responds to environmental conditions is poorly understood. Here, we show that in anoxic Namibian shelf sediments, Lokiarchaeon gene expression levels are higher than those of bacterial phyla and increase with depth below the seafloor. Lokiarchaeon gene expression was significantly different across a hypoxic-sulfidic redox gradient, whereby genes involved in growth, fermentation and H 2 -dependent carbon fixation had the highest expression under the most reducing (sulfidic) conditions. Quantitative stable isotope probing revealed that anaerobic utilization of CO 2 and diatomaceous extracellular polymeric substances by Lokiarchaeon was higher than the bacterial average, consistent with higher expression of Lokiarchaeon genes, including those involved in transport and fermentation of sugars and amino acids. The quantitative stable isotope probing and gene expression data demonstrate homoacetogenic activity of Candidatus Lokiarchaeota, whereby fermentative H 2 production from organic substrates is coupled with the Wood-Ljungdahl carbon fixation pathway 8 . The high energetic efficiency provided by homoacetogenesis 8 helps to explain the elevated metabolic activity of Lokiarchaeon in this anoxic, energy-limited setting.