Antinutritional effects of acorns and tannic acid on the Japanese wood mouse Apodemus speciosus were examined in the laboratory. The first feeding experiment was conducted for 15 days using three types of diet: control diet (laboratory chow for mice), acorns of Quercus serrata (QS), and acorns of Q. mongolica var. grosseserrata (QM), which differ in tannin content (control, tannin free; QS, 2.7% tannic acid equivalent; QM, 8.5%). Six and one of eight mice died in the QM and QS groups, respectively, whereas all mice survived in good health in the control group. Body weight in the QM and QS groups decreased as much as 23.6% and 16.8% in the first 5 days, respectively, whereas that in the control group did not change significantly. Dry matter intake in the QM group was 50.0% and 38.7% less than that in the control and QS, respectively. Apparent dry matter digestibility was not different among the diets, but apparent nitrogen digestibility did differ between the two acorn groups (QM, −17.5%; QS, 12.0%). The logistic regression analyses revealed that the survival of mice was synergistically influenced by both dry matter intake and apparent nitrogen digestibility. In the second experiment, wood mice fed the tannin‐free formula diet, which is nutritionally matched to QS and QM acorns except for the tannin, did not suffer antinutritional effects, whereas mice fed the tannin‐supplemented formula diets suffered body weight loss and negative nitrogen digestibility. These results indicate that the tannins in acorns could cause serious damage to the wood mouse, which may rely on acorns as a usual diet. Plausible hypotheses explaining how the wood mice could overcome the deleterious effects of the acorns are discussed.