Fluid resuscitation with colloids is an established second line therapy for septic patients. Evidence of relative efficacy outcomes is tempered by considerations of the relative costs of the individual fluids. An assessment of recent large clinical trials was performed, resulting in a ranking in the efficacy of these therapies. Probabilities for mortality and the need for renal replacement therapy (RRT) were derived and used to inform a decision analysis model comparing the effect of crystalloid, albumin and hydroxyethyl starch solutions in severe septic patients followed from hospital admission to 90 days in intensive care. The US payer perspective was used. Model inputs for costs and efficacy were derived from the peer-reviewed literature, assuming that that all fluid preparations are bio-equivalent within each class of these therapies. Probabilities for mortality and the need for renal replacement therapy (RRT) data were synthesized using a Bayesian meta-analysis. Relative to crystalloid therapy, 0.21 life years were gained with albumin and 0.85 life years were lost with hydroxyethyl starch. One-way sensitivity analysis showed that the model's outcomes were sensitive to the cost of RRT but not to the costs of the actual fluids or any other costs. We conclude that albumin may be the most cost-effective treatment in these patients when the total medical costs and iatrogenic morbidities involved in treating sepsis with fluids are considered. These results should assist and inform decision making in the choice of these drugs.