Syngas (CO, CO2, and H2) has attracted special attention due to the double benefit of syngas fermentation for carbon sequestration (pollution reduction), while generating energy. Syngas can be either produced by gasification of biomasses or as a by-product of industrial processes. Only few microorganisms, mainly clostridia, were identified as capable of using syngas as a substrate to produce medium chain acids, or alcohols (such as butyric acid, butanol, hexanoic acid, and hexanol). Since CO plays a critical role in the availability of reducing equivalents and carbon conversion, this work assessed the effects of constant CO partial pressure (PCO), ranging from 0.5 to 2.5 atm, on cell growth, acid production, and solvent production, using Clostridium carboxidivorans. Moreover, this work focused on the effect of the liquid to gas volume ratio (VL/VG) on fermentation performances; in particular, two VL/VG were considered (0.28 and 0.92). The main results included—(a) PCO affected the growth kinetics of the microorganism; indeed, C. carboxidivorans growth rate was characterized by CO inhibition within the investigated range of CO concentration, and the optimal PCO was 1.1 atm (corresponding to a dissolved CO concentration of about 25 mg/L) for both VL/VG used; (b) growth differences were observed when the gas-to-liquid volume ratio changed; mass transport phenomena did not control the CO uptake for VL/VG = 0.28; on the contrary, the experimental CO depletion rate was about equal to the transport rate in the case of VL/VG = 0.92.