Iodine and selenium together fulfill important functional roles in organisms of humans and animals. Conducting simultaneous biofortification (enrichment) of plants with these elements is justified as ...combined endemic deficiency of I and Se (hidden hunger) is often encountered. Relatively little is known about the interaction between I and Se in plants, not only with respect to their accumulative efficiency, but also its influence on mineral nutrition or biological quality of crop. The study (conducted in 2012–2014) in-cluded soil fertilization of lettuce cv. ‘Valeska’ with I and Se in the following combina-tions: control, KI, KIO3, Na2SeO4, Na2SeO3, KI + Na2SeO4, KIO3 + Na2SeO4, KI + Na2SeO3, KIO3 + Na2SeO3. Iodine and selenium were applied twice: before sowing and as a top-dressing (each of 2.5 kg I·ha-1 + 0.5 kg Se·ha-1) – a total dose of 5 kg I·ha-1 and 1 kg Se·ha-1 was used. Diversified weather conditions significantly modified the impact fertilization with I and Se had on tested aspects of nitrogen metabolism and biological quality of lettuce – except for the lettuce heads mass and the sucrose content. Based on the results concerning average lettuce weight as well as the level of sugars, phenolic com-pounds, phenylpropanoids, flavonols and antioxidizing activity it was concluded that the application of Na2SeO4 alone or together with iodine acted as a stress factor for cultivated plants.