<p><strong>Abstract.</strong> Studies on the impacts of climate change typically focus on changes to mean conditions. However, animals live in temporally variable environments which give rise to different exposure histories that could affect sensitivities to climate change. Ocean deoxygenation has been observed in nearshore, upper-slope depths in the Southern California Bight, but how these changes compared to the magnitude of natural O<sub>2</sub> variability experienced by seafloor communities at short time-scales was unknown. We aimed to develop a low-cost and spatially flexible approach for studying nearshore, deep-sea ecosystems and monitoring deep-water oxygen variability and benthic community responses. Using a novel, autonomous hand-deployable Nanolander with an SBE MicroCAT and camera system, high-frequency environmental (O<sub>2</sub>, T, pHest) and seafloor community data were collected at depths between 100&#8211;400&#8201;m off San Diego, CA to characterize: timescales of natural environmental variability, changes in O<sub>2</sub> variability with depth, and community responses to O<sub>2</sub> variability. Oxygen variability was strongly linked to tidal processes, and contrary to expectation, oxygen variability did not decline linearly with depth. Depths of 200 and 400&#8201;m showed especially high O<sub>2</sub> variability which may buffer communities at these depths to deoxygenation stress by exposing them to periods of relatively high O<sub>2</sub> conditions across short time-scales (daily and weekly). Despite experiencing high O<sub>2</sub> variability, seafloor communities showed limited responses to changing conditions at these shorter time-scales. Over 5-month timescales, some differences in seafloor communities may have been related to seasonal changes in the O<sub>2</sub> regime. Overall, we found lower oxygen conditions to be associated with a transition from fish-dominated to invertebrate-dominated communities, suggesting this taxonomic shift may be a useful ecological indicator of hypoxia. Due to their small size and ease of use with small boats, hand-deployable Nanolanders can serve as a powerful capacity-building tool in data-poor regions for characterizing environmental variability and examining seafloor community sensitivity to climate-driven changes.</p>