A direct oxidation fuel cell (DOFC) system comprises at least one fuel cell assembly including a cathode and an anode with an electrolyte positioned therebetween; a source of liquid fuel in fluid communication with an anode inlet; an oxidant supply in fluid communication with a cathode inlet; a liquid/gas (L/G) separator in fluid communication with anode and cathode outlets for: (1) receiving unreacted fuel and liquid and gaseous products of electrochemical reactions at the cathode and anode, and (2) supplying the unreacted fuel and liquid product to the inlet of said anode; and a control and/or regulation system for determining a fuel efficiency value of the DOFC system during operation and determining and regulating and/or controlling oxidant stoichiometry of the DOFC system at an appropriate value in response to the determined fuel efficiency value.