A ventilator comprising; (a) a pressure generator configured to generate a pressurized flow of breathable gas for delivery to an airway of the subject; (b) a subject interface configured to guide the pressurized flow of breathable gas to the airway of the subject, wherein the subject interface includes a volume of dead space; (c) one or more sensors configured to generate output signals conveying information related to flow rate and/or pressure in the subject interface; and (d) one or more processors configured to execute computer program modules, the computer program modules comprising: (i) a control module configured to control the pressure generator to generate the pressurized flow of breathable gas to at least partially mechanically ventilate the subject; characterized in that the computer program modules further comprise: (ii) a parameter determination module configured to: determine, based on the output signals generated during an exhalation, an exhaled tidal volume and a leaked exhalation volume, and determine, based on the output signals generated during a subsequent inhalation, an inhaled tidal volume and a leaked inhalation volume; (iii) an estimation module configured to estimate a fraction of inhaled oxygen during the subsequent inhalation based on a first comparison of the exhaled tidal volume with a combination of the volume of dead space and the leaked exhalation volume, and further based on a second comparison of the inhaled tidal volume with a combination of the volume of dead space and the leaked inhalation volume. (a) a pressure generator configured to generate a pressurized flow of breathable gas for delivery to an airway of the subject; (b) a subject interface configured to guide the pressurized flow of breathable gas to the airway of the subject, wherein the subject interface includes a volume of dead space; (c) one or more sensors configured to generate output signals conveying information related to flow rate and/or pressure in the subject interface; and (d) one or more processors configured to execute computer program modules, the computer program modules comprising: (i) a control module configured to control the pressure generator to generate the pressurized flow of breathable gas to at least partially mechanically ventilate the subject; characterized in that the computer program modules further comprise: (ii) a parameter determination module configured to: determine, based on the output signals generated during an exhalation, an exhaled tidal volume and a leaked exhalation volume, and determine, based on the output signals generated during a subsequent inhalation, an inhaled tidal volume and a leaked inhalation volume; (iii) an estimation module configured to estimate a fraction of inhaled oxygen during the subsequent inhalation based on a first comparison of the exhaled tidal volume with a combination of the volume of dead space and the leaked exhalation volume, and further based on a second comparison of the inhaled tidal volume with a combination of the volume of dead space and the leaked inhalation volume. (i) a control module configured to control the pressure generator to generate the pressurized flow of breathable gas to at least partially mechanically ventilate the subject; (ii) a parameter determination module configured to: determine, based on the output signals generated during an exhalation, an exhaled tidal volume and a leaked exhalation volume, and determine, based on the output signals generated during a subsequent inhalation, an inhaled tidal volume and a leaked inhalation volume; determine, based on the output signals generated during an exhalation, an exhaled tidal volume and a leaked exhalation volume, and determine, based on the output signals generated during a subsequent inhalation, an inhaled tidal volume and a leaked inhalation volume; (iii) an estimation module configured to estimate a fraction of inhaled oxygen during the subsequent inhalation based on a first comparison of the exhaled tidal volume with a combination of the volume of dead space and the leaked exhalation volume, and further based on a second comparison of the inhaled tidal volume with a combination of the volume of dead space and the leaked inhalation volume.