Microbial sulfur cycling in marine sediments often occurs in environments characterized by transient chemical gradients that affect both the availability of nutrients and the activity of microbes. High turnover rates of intermediate valence sulfur compounds and the intermittent availability of oxygen in these systems greatly impact the activity of sulfur‐oxidizing micro‐organisms in particular. In this study, the thiosulfate‐oxidizing hydrothermal vent bacterium Thiomicrospira thermophila strain EPR85 was grown in continuous culture at a range of dissolved oxygen concentrations (0.04–1.9 mM) and high pressure (5–10 MPa) in medium buffered at pH 8. Thiosulfate oxidation under these conditions produced tetrathionate, sulfate, and elemental sulfur, in contrast to previous closed‐system experiments at ambient pressure during which thiosulfate was quantitatively oxidized to sulfate. The maximum observed specific growth rate at 5 MPa pressure under unlimited O2 was 0.25 hr−1. This is comparable to the μmax (0.28 hr−1) observed at low pH (<6) at ambient pressure when T. thermophila produces the same mix of sulfur species. The half‐saturation constant for O2 (KO2) estimated from this study was 0.2 mM (at a cell density of 105 cells/ml) and was robust at all pressures tested (0.4–10 MPa), consistent with piezotolerant behavior of this strain. The cell‐specific KO2 was determined to be 1.5 pmol O2/cell. The concentrations of products formed were correlated with oxygen availability, with tetrathionate production in excess of sulfate production at all pressure conditions tested. This study provides evidence for transient sulfur storage during times when substrate concentration exceeds cell‐specific KO2 and subsequent consumption when oxygen dropped below that threshold. These results may be common among sulfur oxidizers in a variety of environments (e.g., deep marine sediments to photosynthetic microbial mats).