The study explored the effect of ambient oxygen on mammalian cell survival after exposure to 10 ns duration, high voltage electrical pulses (nsEP, 80–90 or 120–130 kV/cm; 200–400 pulses per exposure). Cell samples were equilibrated with pure nitrogen, atmospheric air, or pure oxygen prior to the nsEP treatment and were returned to the incubator (air + 5% CO2) shortly after the exposure. The experiments established that survival of hypoxic Jurkat and U937 cells exceeded that of air-equilibrated controls about twofold (P < .01). Conversely, saturation of the medium with oxygen prior to exposure decreased Jurkat cell survival about 1.5 times, P < .01. Attenuation of the cytotoxic effect under hypoxic conditions resembled a well-known effect of oxygen on cell killing by sparsely ionizing radiations and may be indicative of the similarity of underlying cell damage mechanisms. Bioelectromagnetics 27:221–225, 2006. Published 2005 Wiley-Liss, Inc.