Biological nitrogen fixation (BNF) is a sustainable process that dismisses the use of supplemental N-fertilizers in soybean [ Glycine max (L.) Merrill]. Strategies to provide early nodulation may increase the effectiveness of BNF under stressing conditions like drought. We assessed the effects of inoculation of Bradyhizobium , co-inoculation of Bradyrhizobium and Azospirillum , and addition of microbial secondary metabolites (MSM) on nodulation parameters and soybean yield in four field experiments in two growing seasons, 2013/14 and 2014/15, in Southern Brazil. The treatments were: non-inoculated (Ni) control; Ni + N-fertilizer (100 kg ha −1 at sowing and 100 kg ha −1 at full flowering, as urea); Inoculated with Bradyrhizobium (I); Co-inoculated with Bradyrhizobium + Azospirillum brasilense (Co-I); Co-I + microbial secondary metabolites (MSM) and I + MSM. All trials were rainfed and the second trial in 2014/15 was severely affected by drought and high temperatures. The co-inoculation with Azospirillum increased the soybean nodulation at early developmental stages and resulted in higher shoot N accumulation and plant growth, especially under drought. The addition of MSM attenuated the effect of drought on nodulation and in one trial increased the grain yield by 15% and 7% in relation to the N-fertilizer and sole inoculation with Bradyrhizobium , respectively. The strategy of co-inoculation stimulates an early nodulation and helps the maintenance of nodulation under drought; moreover, the addition of MSM improves nodulation and may increase the grain yield. [ABSTRACT FROM AUTHOR]