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Background: Soil acidity, low soil nutrient status and low nitrogen fixing inoculants as a result of poor soil fertility management practices are the major constraints in soybean production in Assosa Zone, particularly in Assosa and Bambassi districts. Hence, this experiment was conducted to evaluate the effect of bio-, organic and inorganic NPSB fertilizers and lime on soil physico-chemical properties. Methods: During the period 2019-2020 factorial combinations of two bio-fertilizer inoculants [without bio-fertilizer (B1) and SB12 plus MAR1495 bio-fertilizer at their recommended rates of 500 g ha-1 (B2); two organic fertilizers without fresh cattle manure (M1) and fresh cattle manure at 10 t ha-1 (M2); two lime rates without lime (L1) and lime at 5 t ha-1 (L2); two inorganic NPSB fertilizers NPSB at 9.5-23-3.5-0.05 (F1) and NPSB at 19-46-7-0.1 (F2) at their recommended rates for soybean] were laid out in a randomized complete block design with three replications. Bulk density, pH, total nitrogen, available phosphorus, organic carbon and cation exchange capacity were collected and analyzed using SAS software version 9.1.3 and significant mean differences were separated using Duncan's multiple range test (DMRT). Result: Bulk density, pH, total nitrogen, available phosphorus, organic carbon and cation exchange capacity were highly affected (P<0.01) by the interactions of bio-, organic and inorganic fertilizers and lime. Finally, the interaction of SB12+MAR1495, 10 t/ha fresh cattie manure, 5 t/ha lime and NPSB at 19-46-7-0.1 improved the bulk density, pH, total nitrogen, available phosphorus, organic carbon and cation exchange capacity at both districts. [ABSTRACT FROM AUTHOR]