<jats:title>Abstract</jats:title><jats:p><jats:bold>Introduction: </jats:bold>Over the last decade HPLC‐NMR has become a robust analytical technique that has been applied to a wide range of studies, particularly plant extracts. There have been only a few applications of the use of HPLC‐NMR to profile marine natural product extracts and no studies involving marine algae. The marine alga selected for this study belongs to the genus <jats:italic>Plocamium</jats:italic>, which is a well known source of polyhalogenated monoterpenes.<jats:p><jats:bold>Objective: </jats:bold>To chemically profile the marine alga <jats:italic>P</jats:italic>.<jats:italic> mertensii</jats:italic>, using a combination of on‐line (HPLC‐NMR) and off‐line approaches.<jats:p><jats:bold>Methodology: </jats:bold><jats:italic>P</jats:italic>.<jats:italic> mertensii</jats:italic> was extracted with 3:1 methanol–dichloromethane and subsequently partitioned into dichloromethane and methanol‐soluble fractions. The methanol partition was exclusively profiled by HPLC‐NMR (on‐flow, stop‐flow and time‐slice experiments) whilst the dichloromethane partition was investigated by conventional isolation and purification procedures.<jats:p><jats:bold>Results: </jats:bold>HPLC‐NMR analysis of the methanol partition partially identified the presence of the major compounds <jats:bold>7</jats:bold>, <jats:bold>13</jats:bold>, <jats:bold>27</jats:bold> and <jats:bold>37</jats:bold>, the structures of which were unequivocally elucidated by off‐line characterisation of the dichloromethane partition. Two additional minor metabolites (<jats:bold>3</jats:bold> and <jats:bold>8</jats:bold>) present in the dichloromethane partition were only tentatively identified as these co‐occurred in a mixture with compounds <jats:bold>7</jats:bold> and <jats:bold>13</jats:bold>. As a result of this study a number of chemical shift reassignments were made for compound <jats:bold>37</jats:bold>.<jats:p><jats:bold>Conclusion: </jats:bold>This is one of the few reports describing the application of HPLC‐NMR to rapidly profile or dereplicate a marine organism and the first application of HPLC‐NMR to successfully profile the chemistry of a marine alga. Copyright © 2008 John Wiley & Sons, Ltd.