Second-order advantage of excitation-emission fluorescence measurements was applied to the simultaneous determination of paracetamol (PC) and mefenamic acid (MF) in urine samples. Two drugs were quantified by multivariate curve resolution coupled to alternative least squares (MCR-ALS) in micellar media of sodium dodesyl sulfate (SDS). Experimental conditions including pH and SDS concentration were optimized. Under the optimum conditions, pH 2.0 and 0.05 mol L(-1) of SDS, paracetamol and mefenamic acid were determined in concentration range 4.00-20.00 microg mL(-1) and 0.80-5.00 microg mL(-1), respectively, in urine samples.