The response of broiler chickens to two levels of endo-1,4-beta xylanase (EC 3.2.1.8) and endo-1,3-beta glucanase (EC 3.2.1.6) combination (with and without), three levels of digestible lysine (0.8%, 0.9% and 1.0% with the applicability of ideal protein concept) and two levels of cottonseed meal (CSM; 20% and 30%) were evaluated in 2 x 3 x 2 factorial arrangement. A total of 2448 male Hubbard broiler chicks were fed on practical vegetable-based mash diets having 2750 kcal metabolizable energy (ME) per kg and 18.5% crude protein (CP) from the age of day 1 to 42. The supplemental enzyme had minimum 1100 units of endo-1,4-beta xylanase and 100 units of endo-1,3-beta glucanase/kg of finished diet. The addition of CSM at 30% resulted in increasing arginine to lysine ratio. A decrease in dressing and breast percentages were observed by the addition of 30% CSM. The digestible lysine at 1.0% decreased the body weight (BW) gain and lowered the mortality during day 1 to 21 whereas the BW gain and feed:gain ratio were unaffected among the three digestible lysine levels during day 1 to 42. The antibody titres against Newcastle and infectious bursal disease viruses were improved with the increasing levels of digestible lysine. The enzyme supplementation improved the apparent ME and digestibility coefficient of nitrogen when it was used with 30% CSM. No effect of enzyme, lysine, CSM or their interactions was observed on serum iron, gizzard and liver weights or abdominal fat percentage. The results showed that increasing digestible lysine improved the antibody titre but did not improve the growth performance and carcass characteristics; supplemental enzyme failed to show any improvement in performance of birds fed on CSM-based diets.