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Low soil fertility is one of the major constraints that limit crop production in sub-Saharan African countries,including Ethiopia. The field experiment was done during 2018/19 cropping season to assess the effects of Mesorhizobium inoculant, Phosphorus (P), and Sulfur (S) on nodulation, growth, nutrient uptake and yield response of chickpea. The experiment was laid out in a randomized complete block design (RCBD) with a factorial combination of Mesorhizobium inoculant (un-inoculated and inoculated), three levels of P (17, 34 and 51 kg/ha) and
three levels of S (7, 14 and 21kg/ha) with three replications, and Haberu variety was used for all the experimental units. All plots received a basal application of 19 kg N/ha uniformly. The analysis of variance showed significant differences for the phenological, nodulation (nodule number and nodule dry weight), growth parameters (shoot dry weight, plant height and number of branches), yield and yield components and nutrient uptake of (N and P) traits in response to the main effects. The highest number (47) and dry weight (460 mg) of nodules per plant were found for the combined application of P (51 kg/ha) with Mesorhizobium inoculant. In addition, the application of 21 kg/ha S with Mesorhizobium inoculant gave 43 nodule number and 450.4 mg nodule dry weight and 13.1 gm shoot dry weight. The highest grain yield (2202.3 kg/ha), total N uptake (71.4 kg/ha), and total P uptake (15.4 kg/ha) were obtained from the application of 51 kg/ha P with Mesorhizobium inoculant. In addition, the highest total S uptake of 21.43 kg/ha was obtained from the application of 51 kg/ha P and 21 kg/ha S. Hence, it can be concluded that application 51 kg P/ha and 21 kg/ha S with inoculant is found to the best treatment combination. Thus, biofertilizer and appropriate fertilizer-P and S management will ensure optimal agronomic and economic returns in the study area.