High solids loadings (>18wt%) in enzymatic hydrolysis and fermentation are desired for lignocellulosic biofuel production at a high titer and low cost. However, sugar conversion and ethanol yield decrease with increasing solids loading. The factor(s) limiting sugar conversion at high solids loading is not clearly understood. In the present study, we investigated the effect of solids loading on simultaneous saccharification and co-fermentation (SSCF) of AFEX (ammonia fiber expansion) pretreated corn stover for ethanol production using a xylose fermenting strain Saccharomyces cerevisiae 424A(LNH-ST). Decreased sugar conversion and ethanol yield with increasing solids loading were also observed. End-product (ethanol) was proven to be the major cause of this issue and increased degradation products with increasing solids loading was also a cause. For the first time, we show that with in situ removal of end-product by performing SSCF aerobically, sugar conversion stopped decreasing with increasing solids loading and monomeric sugar conversion reached as high as 93% at a high solids loading of 24.9wt%. Techno-economic analysis was employed to explore the economic possibilities of cellulosic ethanol production at high solids loadings. The results suggest that low-cost in situ removal of ethanol during SSCF would significantly improve the economics of high solids loading processes. Biotechnol. Bioeng. 2017;114: 980-989. (C) 2016 Wiley Periodicals, Inc.