Introduction. In previous works, the authors proposed a new approach to the calculation of the concentration of toxic products of combustion. The approach is based on determination the volume average density of toxic gases at any given time by using their experimental dependences on the mean volume temperature. The accuracy of this approach depends heavily on the error of determining the heat losses coefficients in small-scale experimental setup and real full scale room. In this paper, using experimental data obtained on small-scale pilot plant, it is proposed a different approach, that uses the theoretical and experimental dependences between average volume densities of toxic gases and the mean volume density of oxygen. It is not necessary to determine the heat losses coefficient and also solve differential equations of the conservation laws of toxic gases masses. Materials and methods. Coniferous wood building materials, transformer oil and PVC sheath cables are considered as combustible materials. Theoretical and experimental methods of gas dynamics and heat and mass transfer are used to determine the parameters of gases mixture during free convection. Theory and calculation. A physical and mathematical model for calculating the mean volume density of carbon monoxide and toxic index for the combined effects of CO and O2 during the combustion of solid and liquid substances and materials in conventionally hermetic volume of arbitrary sizes is proposed. The model is based on the integral method for calculating thermal and gas dynamics of fire in the room. Formulas for calculating the mean volume density of CO and toxicity index for mutual effect of the action of CO and O2 are obtained. Results. Experimental dependencies of mean volume density of carbon monoxide and toxicity index from mean volume density of oxygen are obtained in a small-scale pilot plant. A comparison of the theoretical values of mean volume density of CO and toxicity index derived using the proposed formulas with experimental values is made. Discussion. It is shown that the volume average density of carbon monoxide and the toxicity index for the combined effects of CO and O2 during combustion of solid and liquid materials in conventionally hermetic volume of arbitrary sizes can be calculated by using only the average volume oxygen density and specific coefficients of separation of CO and deleting O2. The resulting formulas for calculating the mean density of CO and toxicity index of the mutual influence of CO and O2 do not contain the geometric sizes of the room and combustible materials surfaces and, therefore, are fair in both small-scale and large-scale fire in the room. Conclusions. The proposed physical and mathematical model allows calculation of mean volume density of CO and toxicity index for combined effects of CO and O2 during fire in a real full-scale room without solving the differential equation of conservation law of carbon monoxide mass and using the experimental dependence between the mean volume densities of CO and O2 and the calculated average volume density of O2.