In this work a second order approach for reliabilitybased design optimization (RBDO) with mixtures of uncorrelated non-Gaussian variables is derived by applying second order reliability methods (SORM) and sequential quadratic programming (SQP). The derivation is performed by introducing intermediate variables defined by the incremental iso-probabilistic transformation at the most probable point (MPP). By using these variables in the Taylor expansions of the constraints, a corresponding general first order reliability method (FORM) based quadratic programming (QP) problem is formulated and solved in the standard normal space. The MPP is found in the physical space in the metric of Hasofer-Lind by using a Newton algorithm, where the efficiency of the Newton method is obtained by introducing an inexact Jacobian and a line-search of Armijo type. The FORM-based SQP approach is then corrected by applying four SORM approaches: Breitung, Hohenbichler, Tvedt and a recent suggested formula. The proposed SORMbased SQP approach for RBDO is accurate, efficient and robust. This is demonstrated by solving several established benchmarks, with values on the target of reliability that are considerable higher than what is commonly used, for mixtures of five different distributions (normal, lognormal, Gumbel, gamma and Weibull). Established benchmarks are also generalized in order to study problems with large number of variables and several constraints. shown that the proposed approach efficiently solves a problem with 300 variables and 240 constraints within less than 20 CPU minutes on a laptop. Finally, a most well-know deterministic benchmark of a welded beam is treated as a RBDO problem using the proposed SORM-based SQP approach.