The feeding value of sun dried Ea ( Eupatorium adenophorum, Ea ) leaves in combination with mulberry ( Morus alba, Ma) was studied by in vitro gas production (IVGP) technique and in vivo feeding experiment with sheep. The IVGP involved both kinetic assay and ruminal fermentation attributes (gas production, CH4, volatile fatty acids (VFA), purines and digestibility parameters). IVGP data from the combined substrates having Ea at 5.0, 7.5, 10.0, 15.0, 20.0, 30.0, 40.0, 50.0 and 100.0% levels with Ma ruminally incubated for 72 h were studied by using single pool Logistic model. The in vitro result was validated in vivo involving eighteen sheep (18 mo, average BW 22.5 ± 1.1 kg) which were randomly distributed in three equal groups. Group 1 served as control and fed with a complete diet having concentrate mixture and wheat straw at 50:50 ratio. In groups 2 and 3, the concentrate was replaced at 50% level with Ma and Ma + Ea (60:40 ratio), respectively. A digestion trial was conducted after 3 months of experimental feeding for assessing feed and nutrient intake and digestibility. The potential gas production (B) revealed an increasing trend up to 40% (from 41.5 to 48.5 ml) accompanied by a decreasing lag (L, from 2.15 to 0.69 h), increase in rate maxima (μ m, from 2.18 to 3.02) and a decrease in halfway time to the maximum gas volume (t 1/2, from 11.73 to 8.72 h) and all these values reversed at higher inclusion levels. CH 4 production showed a declining trend with the increase in Ea in the substrate (20% reduction with 100% Ea). VFA production (mM/g DM) decreased from 3.69 to 2.47 with a consequent decrease in acetate: propionate ratio from 4.39 to 3.14 at Ea 40%. True DM digestibility decreased at Ea higher than 40%. Partitioning factor (PF) and efficiency of microbial protein synthesis also showed an increasing trend up to 40% Ea. The feeding experiment in sheep showed non-significant difference in DM and nutrient intake between the groups, but there was a marked depression (P < 0.001) in digestibility of nutrients when concentrate was replaced with Ma, which declined further with the inclusion of Ea. However, the animals showed positive live weight gain (average daily gain 20 g/d) and the difference from other dietary groups was non-significant. On the basis of positive in vitro ruminal fermentation data (lower total gas, CH 4, VFA, improved acetate: propionate ratio, higher digestibility, microbial protein synthesis, PF) for Ma 60+ Ea40 and in vivo data on the forage mixture with Ea having high CP (223 g/kg DM), moderate intake and OM digestibility (0.599) sustaining minimum live weight gain in sheep, the encroaching eupatorium biomass can partly substitute costly protein concentrates and may have potential to be incorporated in the complete diet. However, long term feeding experiment is warranted to rule out its toxic effect.