Foliar fungicides in wheat are typically used to safeguard against economic losses from diseases. In this study, we assessed the effects of three fungicide spray regimes [single, double, and triple treatments] on four different grain quality parameters [thousand grain weight (TGW), test weight (TW), grain protein content (GPC), and Zeleny sedimentation volume (ZSV)] during the 2006–2009 period at two sites in Luxembourg. The fungicides used were generally a mix of chlorothalonil and triazoles. At Burmerange, (cultivar Cubus), the values of TGW, TW, GPC and ZSV ranged from 38 to 62 g, 67 to 83 kg hl−1, 12.0% to 14.7% dry matter (DM), and 27 to 54 ml, respectively. Whereas, at Everlange (cultivar Achat), the ranges of TGW, TW, GPC and ZSV were 42 to 65 g, 65 to 81 kg hl−1, 11.0% to 15.0% DM, and 21 to 66 ml, respectively. In more than 75% cases, the results indicate that fungicides did not significantly affect TW or ZSV at either sites (P > 0.05). However, there was a significant and positive fungicide effect on GPC in 2006 and 2009 at Burmerange, and only in 2006 at Everlange (P < 0.05). On the contrary, TGW was significantly affected at Burmerange in all years, except 2008 when a positive increase was observed compared to control plots; and in 2006 and 2007 at Everlange. Interestingly, when there was an effect of fungicides on a quality parameter, there was no difference among different fungicide treatments. Thus under conditions prevailing in Luxembourg, a single fungicide treatment applied with judicious timing generally resulted in statistically similar grain quality parameters when compared with a double or triple fungicide treatment.