The hypothesis that a novel endo-beta-mannanase can be used in diets for weanling pigs without negatively impacting growth performance, serum chemistry, hematological characters, or organ weights was tested. A total of 150 newly weaned pigs (75 castrated male and 75 female pigs; initial body weight: 6.20 +/- 0.68 kg) were used. Pigs were allotted to three experimental diets (i.e., control, control plus 800 thermostable mannanase units (TMU)/kg, or control plus 100,000 TMU/kg). Pigs were allotted to pens with 5 pigs per pen for a total of 10 replicate pens per treatment. Pigs were fed phase 1 diets from d 1 to 21, and phase 2 diets from d 22 to 42 post-weaning. Average daily gain (ADG), average daily feed intake (ADFI), and gain:feed (G:F) were calculated. Blood samples from two pigs per pen (one male and one female pig) were collected on d 1, 21, and 42. One pig per pen from the control treatment and two pigs per pen from each of the beta-mannanase treatments were euthanized at the end of the experiment and organs were collected. Data were analyzed using the Proc MIXED procedure of SAS with pen as the experimental unit. Results indicated that for the overall experiment, there were no differences in ADG, ADFI, or final body weight among treatments. However, pigs fed the diet with 100,000 TMU/kg of beta-mannanase had greater (P < 0.05) G:F from d 22 to 42 and for the overall experimental period compared with pigs fed the control diet or the diet with 800 TMU/kg of beta-mannanase. Most serum chemistry markers and blood hematological characters were not different among pigs fed experimental diets and concentrations were within the normal biological range for pigs. However, serum phosphorus was greater (P < 0.05) in pigs fed the diet with 100,000 TMU/kg of beta-mannanase compared with pigs fed the other diets, but red cell distribution width and mean platelet volume were greater (P < 0.05) in pigs fed the control diet compared with pigs fed the control diet + 800 TMU/kg of beta-mannanase. Abnormalities in liver, kidney, spleen, heart, stomach, or the small intestine were not observed, and the weight of these organs was not affected by dietary treatments. In conclusion, pigs fed diets containing 100,000 TMU/kg of beta-mannanase had greater G:F from d 1 to 42 post-weaning compared with pigs fed control diets or the diets with 800 TMU/kg, and beta-mannanase did not negatively impact general health and growth of the pigs even if included at a very high dose. An experiment was conducted to test the hypothesis that pigs tolerate high doses of beta-mannanase without negative impact on growth and health. Newly weaned pigs were allotted to a control diet without mannanase or two diets containing 800 units/kg of beta-mannanase, which is the recommended inclusion rate, or 100,000 units/kg of beta-mannanase. Average daily gain (ADG), average daily feed intake (ADFI) and gain to feed ratio (G:F) were not different among treatments during the initial 21 d post-weaning, but G:F was greater (P < 0.05) in pigs fed the diet containing 100,000 units/kg of beta-mannanase from day 22 to 42 and also from day 1 to 42. However, inclusion of 100,000 units/kg of beta-mannanase had no negative impact on serum chemistry markers or hematological characters. Likewise, the diet containing 100,000 units/kg of mannanase did not result in any abnormalities in kidney, liver, heart, spleen, stomach, or small intestine and dietary treatments did not impact the weight of any organs. Overall, results confirmed the hypothesis for the experiment and the beta-mannanase used in this experiment is safe when added to diets for weanling pigs even if the inclusion rate is higher than the recommended dose.